Dying cell clearance and its impact on the outcome of tumor radiotherapy

Frontiers in Oncology

Volumn 2 SEP, Issue , 2012, Pages

  Lauber, Kirsten ^a   Ernst, Anne ^a   Orth, Michael ^a   Herrmann, Martin ^b   Belka, Claus ^a  

^a UNIVERSITY OF MUNICH   (Germany)

^b UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

Author keywords

Apoptosis; Dying cell clearance; Mitotic catastrophe; Necroptosis; Necrosis; Radiotherapy; Senescence

Indexed keywords

APOPTOSIS; CANCER RADIOTHERAPY; CELL DEATH; CELL PHAGOCYTOSIS; DNA DAMAGE; HUMAN; IMMUNE RESPONSE; IRRADIATION; NECROPTOSIS; NECROSIS; NONHUMAN; PROTEIN PHOSPHORYLATION; REVIEW; SENESCENCE; TREATMENT OUTCOME;

EID: 84877273607     PISSN: None     EISSN: 2234943X     Source Type: Journal    
DOI: 10.3389/fonc.2012.00116     Document Type: Review

References (150)

1. Afshar, G., Jelluma, N., Yang, X., Basila, D., Arvold, N. D., Karlsson, A., Yount, G. L., Dansen, T. B., Koller, E., and Haas-Kogan, D. A. (2006). Radiation-induced caspase-8 mediates p53-independent apoptosis in glioma cells. Cancer Res. 66, 4223-4232.
2. Ahrens, S., Zelenay, S., Sancho, D., Hanc, P., Kjaer, S., Feest, C., Fletcher, G., Durkin, C., Postigo, A., Skehel, M., Batista, F., Thompson, B., Way, M., Reis E Sousa, C., and Schulz, O. (2012). F-actin is an evolutionarily conserved damage-associated molecular pattern recognized by DNGR-1, a receptor for dead cells. Immunity 36, 635-645.
3. Albert, M. L., Pearce, S. F., Francisco, L. M., Sauter, B., Roy, P., Silverstein, R. L., and Bhardwaj, N. (1998). Immature dendritic cells phagocytose apoptotic cells via alphavbeta5 and CD36, and cross-present antigens to cytotoxic T lymphocytes. J. Exp. Med. 188, 1359-1368.
4. Anderson, H. A., Maylock, C. A., Williams, J. A., Paweletz, C. P., Shu, H., and Shacter, E. (2003). Serum-derived protein S binds to phosphatidylserine and stimulates the phagocytosis of apoptotic cells. Nat. Immunol. 4, 87-91.
5. Apetoh, L., Ghiringhelli, F., Tesniere, A., Criollo, A., Ortiz, C., Lidereau, R., Mariette, C., Chaput, N., Mira, J. P., Delaloge, S., Andre, F., Tursz, T., Kroemer, G., and Zitvogel, L. (2007). The interaction between HMGB1 and TLR4 dictates the outcome of anticancer chemotherapy and radiotherapy. Immunol. Rev. 220, 47-59.
6. Arur, S., Uche, U. E., Rezaul, K., Fong, M., Scranton, V., Cowan, A. E., Mohler, W., and Han, D. K. (2003). Annexin I is an endogenous ligand that mediates apoptotic cell engulfment. Dev. Cell 4, 587-598.
7. Aymeric, L., Apetoh, L., Ghiringhelli, F., Tesniere, A., Martins, I., Kroemer, G., Smyth, M. J., and Zitvogel, L. (2010). Tumor cell death and ATP release prime dendritic cells and efficient anticancer immunity. Cancer Res. 70, 855-858.
8. Baumann, I., Kolowos, W., Voll, R. E., Manger, B., Gaipl, U., Neuhuber, W. L., Kirchner, T., Kalden, J. R., and Herrmann, M. (2002). Impaired uptake of apoptotic cells into tingible body macrophages in germinal centers of patients with systemic lupus erythematosus. Arthritis Rheum. 46, 191-201.
9. Belka, C., Marini, P., Budach, W., Schulze-Osthoff, K., Lang, F., Gulbins, E., and Bamberg, M. (1998). Radiation-induced apoptosis in human lymphocytes and lymphoma cells critically relies on the up-regulation of CD95/Fas/APO-1 ligand. Radiat. Res. 149, 588-595.
10. Bianchi, M. E., and Manfredi, A. A. (2007). High-mobility group box 1 (HMGB1) protein at the crossroads between innate and adaptive immunity. Immunol. Rev. 220, 35-46.
11. Biswas, S. K., and Mantovani, A. (2010). Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat. Immunol. 11, 889-896.
12. Blander, J. M. (2008). Phagocytosis and antigen presentation: a partnership initiated by Toll-like receptors. Ann. Rheum. Dis. 67(Suppl. 3), iii44-iii49.
13. Blume, K. E., Soeroes, S., Keppeler, H., Stevanovic, S., Kretschmer, D., Rautenberg, M., Wesselborg, S., and Lauber, K. (2012). Cleavage of annexin A1 by ADAM10 during secondary necrosis generates a monocytic "find-me" signal. J. Immunol. 188, 135-145.
14. Blume, K. E., Soeroes, S., Waibel, M., Keppeler, H., Wesselborg, S., Herrmann, M., Schulze-Osthoff, K., and Lauber, K. (2009). Cell surface externalization of annexin A1 as a failsafe mechanism preventing inflammatory responses during secondary necrosis. J. Immunol. 183, 8138-8147.
15. Bondanza, A., Zimmermann, V. S., Rovere-Querini, P., Turnay, J., Dumitriu, I. E., Stach, C. M., Voll, R. E., Gaipl, U. S., Bertling, W., Poschl, E., Kalden, J. R., Manfredi, A. A., and Herrmann, M. (2004). Inhibition of phosphatidylserine recognition heightens the immunogenicity of irradiated lymphoma cells in vivo. J. Exp. Med. 200, 1157-1165.
16. Bottcher, A., Gaipl, U. S., Furnrohr, B. G., Herrmann, M., Girkontaite, I., Kalden, J. R., and Voll, R. E. (2006). Involvement of phosphatidylserine, alphavbeta3, CD14, CD36, and complement C1q in the phagocytosis of primary necrotic lymphocytes by macrophages. Arthritis Rheum. 54, 927-938.
17. Botto, M. (1998). C1q knock-out mice for the study of complement deficiency in autoimmune disease. Exp. Clin. Immunogenet. 15, 231-234.
18. Bournazou, I., Pound, J. D., Duffin, R., Bournazos, S., Melville, L. A., Brown, S. B., Rossi, A. G., and Gregory, C. D. (2009). Apoptotic human cells inhibit migration of granulocytes via release of lactoferrin. J. Clin. Invest. 119, 20-32.
19. Brouckaert, G., Kalai, M., Krysko, D. V., Saelens, X., Vercammen, D., Ndlovu, M. N., Haegeman, G., D'Herde, K., and Vandenabeele, P. (2004). Phagocytosis of necrotic cells by macrophages is phosphatidylserine dependent and does not induce inflammatory cytokine production. Mol. Biol. Cell 15, 1089-1100.
20. Brown, S., Heinisch, I., Ross, E., Shaw, K., Buckley, C. D., and Savill, J. (2002). Apoptosis disables CD31-mediated cell detachment from phagocytes promoting binding and engulfment. Nature 418, 200-203.
21. Burnette, B. C., Liang, H., Lee, Y., Chlewicki, L., Khodarev, N. N., Weichselbaum, R. R., Fu, Y. X., and Auh, S. L. (2011). The efficacy of radiotherapy relies upon induction of type I interferon-dependent innate and adaptive immunity. Cancer Res. 71, 2488-2496.
22. Castano, A. P., Mroz, P., and Hamblin, M. R. (2006). Photodynamic therapy and anti-tumour immunity. Nat. Rev. Cancer 6, 535-545.
23. Castano, A. P., Mroz, P., Wu, M. X., and Hamblin, M. R. (2008). Photodynamic therapy plus low-dose cyclophosphamide generates antitumor immunity in a mouse model. Proc. Natl. Acad. Sci. U.S.A. 105, 5495-5500.
24. Chalaris, A., Rabe, B., Paliga, K., Lange, H., Laskay, T., Fielding, C. A., Jones, S. A., Rose-John, S., and Scheller, J. (2007). Apoptosis is a natural stimulus of IL6R shedding and contributes to the proinflammatory trans-signaling function of neutrophils. Blood 110, 1748-1755.
25. Chen, X., Doffek, K., Sugg, S. L., and Shilyansky, J. (2004). Phosphatidylserine regulates the maturation of human dendritic cells. J. Immunol. 173, 2985-2994.
26. Cohen, P. L., Caricchio, R., Abraham, V., Camenisch, T. D., Jennette, J. C., Roubey, R. A., Earp, H. S., Matsushima, G., and Reap, E. A. (2002). Delayed apoptotic cell clearance and lupus-like autoimmunity in mice lacking the c-mer membrane tyrosine kinase. J. Exp. Med. 196, 135-140.
27. Coppe, J. P., Desprez, P. Y., Krtolica, A., and Campisi, J. (2010). The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu. Rev. Pathol. 5, 99-118.
28. Debatin, K. M., and Krammer, P. H. (2004). Death receptors in chemotherapy and cancer. Oncogene 23, 2950-2966.
29. Deng, Y., and Tsao, B. P. (2010). Genetic susceptibility to systemic lupus erythematosus in the genomic era. Nat. Rev. Rheumatol. 6, 683-692.
30. Diamond, M. S., Kinder, M., Matsushita, H., Mashayekhi, M., Dunn, G. P., Archambault, J. M., Lee, H., Arthur, C. D., White, J. M., Kalinke, U., Murphy, K. M., and Schreiber, R. D. (2011). Type I interferon is selectively required by dendritic cells for immune rejection of tumors. J. Exp. Med. 208, 1989-2003.
31. Doffek, K., Chen, X., Sugg, S. L., and Shilyansky, J. (2011). Phosphatidylserine inhibits NFκB and p38 MAPK activation in human monocyte derived dendritic cells. Mol. Immunol. 48, 1771-1777.
32. Dunn, G. P., Koebel, C. M., and Schreiber, R. D. (2006). Interferons, immunity and cancer immunoediting. Nat. Rev. Immunol. 6, 836-848.
33. Elliott, M. R., Chekeni, F. B., Trampont, P. C., Lazarowski, E. R., Kadl, A., Walk, S. F., Park, D., Woodson, R. I., Ostankovich, M., Sharma, P., Lysiak, J. J., Harden, T. K., Leitinger, N., and Ravichandran, K. S. (2009). Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. Nature 461, 282-286.
34. Eriksson, D., and Stigbrand, T. (2010). Radiation-induced cell death mechanisms. Tumour Biol. 31, 363-372.
35. Eue, I., Pietz, B., Storck, J., Klempt, M., and Sorg, C. (2000). Transendothelial migration of 27E10+ human monocytes. Int. Immunol. 12, 1593-1604.
36. Fadok, V. A., Bratton, D. L., Konowal, A., Freed, P. W., Westcott, J. Y., and Henson, P. M. (1998). Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF. J. Clin. Invest. 101, 890-898.
37. Fadok, V. A., Voelker, D. R., Campbell, P. A., Cohen, J. J., Bratton, D. L., and Henson, P. M. (1992). Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. J. Immunol. 148, 2207-2216.
38. Fan, X., Krahling, S., Smith, D., Williamson, P., and Schlegel, R. A. (2004). Macrophage surface expression of annexins I and II in the phagocytosis of apoptotic lymphocytes. Mol. Biol. Cell 15, 2863-2872.
39. Frey, B., Schildkopf, P., Rodel, F., Weiss, E. M., Munoz, L. E., Herrmann, M., Fietkau, R., and Gaipl, U. S. (2009). AnnexinA5 renders dead tumor cells immunogenic-implications for multimodal cancer therapies. J. Immunotoxicol. 6, 209-216.
40. Frisoni, L., Mcphie, L., Kang, S. A., Monestier, M., Madaio, M., Satoh, M., and Caricchio, R. (2007). Lack of chromatin and nuclear fragmentation in vivo impairs the production of lupus anti-nuclear antibodies. J. Immunol. 179, 7959-7966.
41. Fuertes, M. B., Kacha, A. K., Kline, J., Woo, S. R., Kranz, D. M., Murphy, K. M., and Gajewski, T. F. (2011). Host type I IFN signals are required for antitumor CD8+ T cell responses through CD8{alpha}+ dendritic cells. J. Exp. Med. 208, 2005-2016.
42. Gaipl, U. S., Kuenkele, S., Voll, R. E., Beyer, T. D., Kolowos, W., Heyder, P., Kalden, J. R., and Herrmann, M. (2001). Complement binding is an early feature of necrotic and a rather late event during apoptotic cell death. Cell Death Differ. 8, 327-334.
43. Gaipl, U. S., Munoz, L. E., Grossmayer, G., Lauber, K., Franz, S., Sarter, K., Voll, R. E., Winkler, T., Kuhn, A., Kalden, J., Kern, P., and Herrmann, M. (2007a). Clearance deficiency and systemic lupus erythematosus (SLE). J. Autoimmun. 28, 114-121.
44. Gaipl, U. S., Munoz, L. E., Rodel, F., Pausch, F., Frey, B., Brachvogel, B., Von Der Mark, K., and Poschl, E. (2007b). Modulation of the immune system by dying cells and the phosphatidylserine-ligand annexin A5. Autoimmunity 40, 254-259.
45. Gaipl, U. S., Voll, R. E., Sheriff, A., Franz, S., Kalden, J. R., and Herrmann, M. (2005). Impaired clearance of dying cells in systemic lupus erythematosus. Autoimmun. Rev. 4, 189-194.
46. Galluzzi, L., Vitale, I., Abrams, J. M., Alnemri, E. S., Baehrecke, E. H., Blagosklonny, M. V., Dawson, T. M., Dawson, V. L., El-Deiry, W. S., Fulda, S., Gottlieb, E., Green, D. R., Hengartner, M. O., Kepp, O., Knight, R. A., Kumar, S., Lipton, S. A., Lu, X., Madeo, F., Malorni, W., Mehlen, P., Nunez, G., Peter, M. E., Piacentini, M., Rubinsztein, D. C., Shi, Y., Simon, H. U., Vandenabeele, P., White, E., Yuan, J., Zhivotovsky, B., Melino, G., and Kroemer, G. (2012). Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012. Cell Death Differ. 19, 107-120.
47. Garaude, J., Kent, A., Van Rooijen, N., and Blander, J. M. (2012). Simultaneous targeting of Toll-and nod-like receptors induces effective tumor-specific immune responses. Sci. Transl. Med. 4, 120ra116.
48. Gardai, S. J., Mcphillips, K. A., Frasch, S. C., Janssen, W. J., Starefeldt, A., Murphy-Ullrich, J. E., Bratton, D. L., Oldenborg, P. A., Michalak, M., and Henson, P. M. (2005). Cell-surface calreticulin initiates clearance of viable or apoptotic cells through trans-activation of LRP on the phagocyte. Cell 123, 321-334.
49. Gehrmann, M., Liebisch, G., Schmitz, G., Anderson, R., Steinem, C., De Maio, A., Pockley, G., and Multhoff, G. (2008). Tumor-specific Hsp70 plasma membrane localization is enabled by the glycosphingolipid Gb3. PLoS ONE 3, e1925. doi: 10.1371/journal.pone.0001925
50. Ghiringhelli, F., Apetoh, L., Tesniere, A., Aymeric, L., Ma, Y., Ortiz, C., Vermaelen, K., Panaretakis, T., Mignot, G., Ullrich, E., Perfettini, J. L., Schlemmer, F., Tasdemir, E., Uhl, M., Genin, P., Civas, A., Ryffel, B., Kanellopoulos, J., Tschopp, J., Andre, F., Lidereau, R., Mclaughlin, N. M., Haynes, N. M., Smyth, M. J., Kroemer, G., and Zitvogel, L. (2009). Activation of the NLRP3 inflammasome in dendritic cells induces IL-1beta-dependent adaptive immunity against tumors. Nat. Med. 15, 1170-1178.
51. Grossmayer, G. E., Munoz, L. E., Weber, C. K., Franz, S., Voll, R. E., Kern, P. M., Kalden, J. R., Schett, G., Herrmann, M., and Gaipl, U. S. (2008). IgG autoantibodies bound to surfaces of necrotic cells and complement C4 comprise the phagocytosis promoting activity for necrotic cells of systemic lupus erythaematosus sera. Ann. Rheum. Dis. 67, 1626-1632.
52. Gude, D. R., Alvarez, S. E., Paugh, S. W., Mitra, P., Yu, J., Griffiths, R., Barbour, S. E., Milstien, S., and Spiegel, S. (2008). Apoptosis induces expression of sphingosine kinase 1 to release sphingosine-1-phosphate as a "come-and-get-me" signal. FASEB J. 22, 2629-2638.
53. Hanayama, R., Miyasaka, K., Nakaya, M., and Nagata, S. (2006). MFG-E8-dependent clearance of apoptotic cells, and autoimmunity caused by its failure. Curr. Dir. Autoimmun. 9, 162-172.
54. Hanayama, R., Tanaka, M., Miwa, K., Shinohara, A., Iwamatsu, A., and Nagata, S. (2002). Identification of a factor that links apoptotic cells to phagocytes. Nature 417, 182-187.
55. Haupt, S., Berger, M., Goldberg, Z., and Haupt, Y. (2003). Apoptosis-the p53 network. J. Cell Sci. 116, 4077-4085.
56. He, J., Yin, Y., Luster, T. A., Watkins, L., and Thorpe, P. E. (2009a). Antiphosphatidylserine antibody combined with irradiation damages tumor blood vessels and induces tumor immunity in a rat model of glioblastoma. Clin. Cancer Res. 15, 6871-6880.
57. He, S., Wang, L., Miao, L., Wang, T., Du, F., Zhao, L., and Wang, X. (2009b). Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha. Cell 137, 1100-1111.
58. Herrmann, M., Voll, R. E., Zoller, O. M., Hagenhofer, M., Ponner, B. B., and Kalden, J. R. (1998). Impaired phagocytosis of apoptotic cell material by monocyte-derived macrophages from patients with systemic lupus erythematosus. Arthritis Rheum. 41, 1241-1250.
59. Hou, Y., Plett, P. A., Ingram, D. A., Rajashekhar, G., Orschell, C. M., Yoder, M. C., March, K. L., and Clauss, M. (2006). Endothelial-monocyte-activating polypeptide II induces migration of endothelial progenitor cells via the chemokine receptor CXCR3. Exp. Hematol. 34, 1125-1132.
60. Huang, Q., Li, F., Liu, X., Li, W., Shi, W., Liu, F. F., O'Sullivan, B., He, Z., Peng, Y., Tan, A. C., Zhou, L., Shen, J., Han, G., Wang, X. J., Thorburn, J., Thorburn, A., Jimeno, A., Raben, D., Bedford, J. S., and Li, C. Y. (2011). Caspase 3-mediated stimulation of tumor cell repopulation during cancer radiotherapy. Nat. Med. 17, 860-866.
61. Hurley, P. J., and Bunz, F. (2007). ATM and ATR: components of an integrated circuit. Cell Cycle 6, 414-417.
62. Huynh, M. L., Fadok, V. A., and Henson, P. M. (2002). Phosphatidylserine-dependent ingestion of apoptotic cells promotes TGF-beta1 secretion and the resolution of inflammation. J. Clin. Invest. 109, 41-50.
63. Iborra, S., Izquierdo, H. M., Martinez-Lopez, M., Blanco-Menendez, N., Reis, E. S. C., and Sancho, D. (2012). The DC receptor DNGR-1 mediates cross-priming of CTLs during vaccinia virus infection in mice. J. Clin. Invest. 122, 1628-1643.
64. Idoyaga, J., Lubkin, A., Fiorese, C., Lahoud, M. H., Caminschi, I., Huang, Y., Rodriguez, A., Clausen, B. E., Park, C. G., Trumpfheller, C., and Steinman, R. M. (2011). Comparable T helper 1 (Th1) and CD8 T-cell immunity by targeting HIV gag p24 to CD8 dendritic cells within antibodies to Langerin, DEC205, and Clec9A. Proc. Natl. Acad. Sci. U.S.A. 108, 2384-2389.
65. Ishimoto, Y., Ohashi, K., Mizuno, K., and Nakano, T. (2000). Promotion of the uptake of PS liposomes and apoptotic cells by a product of growth arrest-specific gene, gas6. J. Biochem. 127, 411-417.
66. Jackson, S. P., and Bartek, J. (2009). The DNA-damage response in human biology and disease. Nature 461, 1071-1078.
67. Kammerer, R., Buchner, A., Palluch, P., Pongratz, T., Oboukhovskij, K., Beyer, W., Johansson, A., Stepp, H., Baumgartner, R., and Zimmermann, W. (2011). Induction of immune mediators in glioma and prostate cancer cells by non-lethal photodynamic therapy. PLoS ONE 6, e21834. doi: 10.1371/journal.pone.0021834
68. Kang, T. W., Yevsa, T., Woller, N., Hoenicke, L., Wuestefeld, T., Dauch, D., Hohmeyer, A., Gereke, M., Rudalska, R., Potapova, A., Iken, M., Vucur, M., Weiss, S., Heikenwalder, M., Khan, S., Gil, J., Bruder, D., Manns, M., Schirmacher, P., Tacke, F., Ott, M., Luedde, T., Longerich, T., Kubicka, S., and Zender, L. (2011). Senescence surveillance of pre-malignant hepatocytes limits liver cancer development. Nature 479, 547-551.
69. Kawane, K., Ohtani, M., Miwa, K., Kizawa, T., Kanbara, Y., Yoshioka, Y., Yoshikawa, H., and Nagata, S. (2006). Chronic polyarthritis caused by mammalian DNA that escapes from degradation in macrophages. Nature 443, 998-1002.
70. Kobayashi, N., Karisola, P., Pena-Cruz, V., Dorfman, D. M., Jinushi, M., Umetsu, S. E., Butte, M. J., Nagumo, H., Chernova, I., Zhu, B., Sharpe, A. H., Ito, S., Dranoff, G., Kaplan, G. G., Casasnovas, J. M., Umetsu, D. T., Dekruyff, R. H., and Freeman, G. J. (2007). TIM-1 and TIM-4 glycoproteins bind phosphatidylserine and mediate uptake of apoptotic cells. Immunity 27, 927-940.
71. Krahling, S., Callahan, M. K., Williamson, P., and Schlegel, R. A. (1999). Exposure of phosphatidylserine is a general feature in the phagocytosis of apoptotic lymphocytes by macrophages. Cell Death Differ. 6, 183-189.
72. Krysko, D. V., Denecker, G., Festjens, N., Gabriels, S., Parthoens, E., D'Herde, K., and Vandenabeele, P. (2006). Macrophages use different internalization mechanisms to clear apoptotic and necrotic cells. Cell Death Differ. 13, 2011-2022.
73. Kuilman, T., and Peeper, D. S. (2009). Senescence-messaging secretome: SMS-ing cellular stress. Nat. Rev. Cancer 9, 81-94.
74. Lauber, K., Blumenthal, S. G., Waibel, M., and Wesselborg, S. (2004). Clearance of apoptotic cells: getting rid of the corpses. Mol. Cell 14, 277-287.
75. Lauber, K., Bohn, E., Krober, S. M., Xiao, Y. J., Blumenthal, S. G., Lindemann, R. K., Marini, P., Wiedig, C., Zobywalski, A., Baksh, S., Xu, Y., Autenrieth, I. B., Schulze-Osthoff, K., Belka, C., Stuhler, G., and Wesselborg, S. (2003). Apoptotic cells induce migration of phagocytes via caspase-3-mediated release of a lipid attraction signal. Cell 113, 717-730.
76. Lauber, K., Munoz, L. E., Berens, C., Jendrossek, V., Belka, C., and Herrmann, M. (2011). Apoptosis induction and tumor cell repopulation: the yin and yang of radiotherapy. Radiat. Oncol. 6, 176.
77. Le, L. Q., Kabarowski, J. H., Weng, Z., Satterthwaite, A. B., Harvill, E. T., Jensen, E. R., Miller, J. F., and Witte, O. N. (2001). Mice lacking the orphan G protein-coupled receptor G2A develop a late-onset autoimmune syndrome. Immunity 14, 561-571.
78. Lee, Y., Auh, S. L., Wang, Y., Burnette, B., Meng, Y., Beckett, M., Sharma, R., Chin, R., Tu, T., Weichselbaum, R. R., and Fu, Y. X. (2009). Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment. Blood 114, 589-595.
79. Levine, A. J. (1997). p53, the cellular gatekeeper for growth and division. Cell 88, 323-331.
80. Liu, L., Yang, M., Kang, R., Wang, Z., Zhao, Y., Yu, Y., Xie, M., Yin, X., Livesey, K. M., Lotze, M. T., Tang, D., and Cao, L. (2011a). HMGB1-induced autophagy promotes chemotherapy resistance in leukemia cells. Leukemia 25, 23-31.
81. Liu, L., Yang, M., Kang, R., Wang, Z., Zhao, Y., Yu, Y., Xie, M., Yin, X., Livesey, K. M., Loze, M. T., Tang, D., and Cao, L. (2011b). DAMP-mediated autophagy contributes to drug resistance. Autophagy 7, 112-114.
82. Lotze, M. T., Zeh, H. J., Rubartelli, A., Sparvero, L. J., Amoscato, A. A., Washburn, N. R., Devera, M. E., Liang, X., Tor, M., and Billiar, T. (2007). The grateful dead: damage-associated molecular pattern molecules and reduction/oxidation regulate immunity. Immunol. Rev. 220, 60-81.
83. Lu, Q., and Lemke, G. (2001). Homeostatic regulation of the immune system by receptor tyrosine kinases of the Tyro 3 family. Science 293, 306-311.
84. Lugade, A. A., Moran, J. P., Gerber, S. A., Rose, R. C., Frelinger, J. G., and Lord, E. M. (2005). Local radiation therapy of B16 melanoma tumors increases the generation of tumor antigen-specific effector cells that traffic to the tumor. J. Immunol. 174, 7516-7523.
85. Lugade, A. A., Sorensen, E. W., Gerber, S. A., Moran, J. P., Frelinger, J. G., and Lord, E. M. (2008). Radiation-induced IFN-gamma production within the tumor microenvironment influences antitumor immunity. J. Immunol. 180, 3132-3139.
86. Maiti, S. N., Balasubramanian, K., Ramoth, J. A., and Schroit, A. J. (2008). Beta-2-glycoprotein 1-dependent macrophage uptake of apoptotic cells. Binding to lipoprotein receptor-related protein receptor family members. J. Biol. Chem. 283, 3761-3766.
87. Manfredi, A. A., Rovere, P., Galati, G., Heltai, S., Bozzolo, E., Soldini, L., Davoust, J., Balestrieri, G., Tincani, A., and Sabbadini, M. G. (1998). Apoptotic cell clearance in systemic lupus erythematosus. I. Opsonization by antiphospholipid antibodies. Arthritis Rheum. 41, 205-214.
88. Mantel, F., Frey, B., Haslinger, S., Schildkopf, P., Sieber, R., Ott, O. J., Lodermann, B., Rodel, F., Sauer, R., Fietkau, R., and Gaipl, U. S. (2010). Combination of ionising irradiation and hyperthermia activates programmed apoptotic and necrotic cell death pathways in human colorectal carcinoma cells. Strahlenther. Onkol. 186, 587-599.
89. Marshak-Rothstein, A. (2006). Toll-like receptors in systemic autoimmune disease. Nat. Rev. Immunol. 6, 823-835.
90. Matzinger, P. (1998). An innate sense of danger. Semin. Immunol. 10, 399-415.
91. McGaha, T. L., Chen, Y., Ravishankar, B., Van Rooijen, N., and Karlsson, M. C. (2011). Marginal zone macrophages suppress innate and adaptive immunity to apoptotic cells in the spleen. Blood 117, 5403-5412.
92. Meek, D. W. (2009). Tumour suppression by p53: a role for the DNA damage response? Nat. Rev. Cancer 9, 714-723.
93. Miyanishi, M., Tada, K., Koike, M., Uchiyama, Y., Kitamura, T., and Nagata, S. (2007). Identification of Tim4 as a phosphatidylserine receptor. Nature 450, 435-439.
94. Morak, M. J., Van Koetsveld, P. M., Kanaar, R., Hofland, L. J., and Van Eijck, C. H. (2011). Type I interferons as radiosensitisers for pancreatic cancer. Eur. J. Cancer 47, 1938-1945.
95. Munoz, L. E., Franz, S., Pausch, F., Furnrohr, B., Sheriff, A., Vogt, B., Kern, P. M., Baum, W., Stach, C., Von Laer, D., Brachvogel, B., Poschl, E., Herrmann, M., and Gaipl, U. S. (2007a). The influence on the immunomodulatory effects of dying and dead cells of Annexin V. J. Leukoc. Biol. 81, 6-14.
96. Munoz, L. E., Frey, B., Pausch, F., Baum, W., Mueller, R. B., Brachvogel, B., Poschl, E., Rodel, F., Von Der Mark, K., Herrmann, M., and Gaipl, U. S. (2007b). The role of annexin A5 in the modulation of the immune response against dying and dead cells. Curr. Med. Chem. 14, 271-277.
97. Munoz, L. E., Lauber, K., Schiller, M., Manfredi, A. A., and Herrmann, M. (2010a). The role of defective clearance of apoptotic cells in systemic autoimmunity. Nat. Rev. Rheumatol. 6, 280-289.
98. Munoz, L. E., Peter, C., Herrmann, M., Wesselborg, S., and Lauber, K. (2010b). Scent of dying cells: the role of attraction signals in the clearance of apoptotic cells and its immunological consequences. Autoimmun. Rev. 9, 425-430.
99. Nakayama, M., Akiba, H., Takeda, K., Kojima, Y., Hashiguchi, M., Azuma, M., Yagita, H., and Okumura, K. (2009). Tim-3 mediates phagocytosis of apoptotic cells and cross-presentation. Blood 113, 3821-3830.
100. Nardella, C., Clohessy, J. G., Alimonti, A., and Pandolfi, P. P. (2011). Pro-senescence therapy for cancer treatment. Nat. Rev. Cancer 11, 503-511.
101. Nishiura, H., Shibuya, Y., and Yamamoto, T. (1998). S19 ribosomal protein cross-linked dimer causes monocyte-predominant infiltration by means of molecular mimicry to complement C5a. Lab. Invest. 78, 1615-1623.
102. Park, D., Tosello-Trampont, A. C., Elliott, M. R., Lu, M., Haney, L. B., Ma, Z., Klibanov, A. L., Mandell, J. W., and Ravichandran, K. S. (2007). BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module. Nature 450, 430-434.
103. Park, S. Y., Jung, M. Y., Kim, H. J., Lee, S. J., Kim, S. Y., Lee, B. H., Kwon, T. H., Park, R. W., and Kim, I. S. (2008). Rapid cell corpse clearance by stabilin-2, a membrane phosphatidylserine receptor. Cell Death Differ. 15, 192-201.
104. Park, S. Y., Jung, M. Y., Lee, S. J., Kang, K. B., Gratchev, A., Riabov, V., Kzhyshkowska, J., and Kim, I. S. (2009). Stabilin-1 mediates phosphatidylserine-dependent clearance of cell corpses in alternatively activated macrophages. J. Cell Sci. 122, 3365-3373.
105. Peter, C., Waibel, M., Radu, C. G., Yang, L. V., Witte, O. N., Schulze-Osthoff, K., Wesselborg, S., and Lauber, K. (2008). Migration to apoptotic "find-me" signals is mediated via the phagocyte receptor G2A. J. Biol. Chem. 283, 5296-5305.
106. Peter, C., Wesselborg, S., Herrmann, M., and Lauber, K. (2010). Dangerous attraction: phagocyte recruitment and danger signals of apoptotic and necrotic cells. Apoptosis 15, 1007-1028.
107. Ran, S., He, J., Huang, X., Soares, M., Scothorn, D., and Thorpe, P. E. (2005). Antitumor effects of a monoclonal antibody that binds anionic phospholipids on the surface of tumor blood vessels in mice. Clin. Cancer Res. 11, 1551-1562.
108. Ravichandran, K. S. (2010). Find-me and eat-me signals in apoptotic cell clearance: progress and conundrums. J. Exp. Med. 207, 1807-1817.
109. Ravichandran, K. S. (2011). Beginnings of a good apoptotic meal: the find-me and eat-me signaling pathways. Immunity 35, 445-455.
110. Reed, J. C. (2006). Drug insight: cancer therapy strategies based on restoration of endogenous cell death mechanisms. Nat. Clin. Pract. Oncol. 3, 388-398.
111. Reits, E. A., Hodge, J. W., Herberts, C. A., Groothuis, T. A., Chakraborty, M., Wansley, E. K., Camphausen, K., Luiten, R. M., De Ru, A. H., Neijssen, J., Griekspoor, A., Mesman, E., Verreck, F. A., Spits, H., Schlom, J., Van Veelen, P., and Neefjes, J. J. (2006). Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy. J. Exp. Med. 203, 1259-1271.
112. Rothlin, C. V., Ghosh, S., Zuniga, E. I., Oldstone, M. B., and Lemke, G. (2007). TAM receptors are pleiotropic inhibitors of the innate immune response. Cell 131, 1124-1136.
113. Rovere-Querini, P., Capobianco, A., Scaffidi, P., Valentinis, B., Catalanotti, F., Giazzon, M., Dumitriu, I. E., Muller, S., Iannacone, M., Traversari, C., Bianchi, M. E., and Manfredi, A. A. (2004). HMGB1 is an endogenous immune adjuvant released by necrotic cells. EMBO Rep. 5, 825-830.
114. Rudner, J., Belka, C., Marini, P., Wagner, R. J., Faltin, H., Lepple-Wienhues, A., Bamberg, M., and Budach, W. (2001). Radiation sensitivity and apoptosis in human lymphoma cells. Int. J. Radiat. Biol. 77, 1-11.
115. Sancho, D., Joffre, O. P., Keller, A. M., Rogers, N. C., Martinez, D., Hernanz-Falcon, P., Rosewell, I., Reis, E., and Sousa, C. (2009). Identification of a dendritic cell receptor that couples sensing of necrosis to immunity. Nature 458, 899-903.
116. Sarmiento, L. F., Munoz, L. E., Chirinos, P., Bianco, N. E., and Zabaleta-Lanz, M. E. (2007). Opsonization by anti-dsDNA antibodies of apoptotic cells in systemic lupus erythematosus. Autoimmunity 40, 337-339.
117. Schildkopf, P., Frey, B., Mantel, F., Ott, O. J., Weiss, E. M., Sieber, R., Janko, C., Sauer, R., Fietkau, R., and Gaipl, U. S. (2010). Application of hyperthermia in addition to ionizing irradiation fosters necrotic cell death and HMGB1 release of colorectal tumor cells. Biochem. Biophys. Res. Commun. 391, 1014-1020.
118. Schildkopf, P., Frey, B., Ott, O. J., Rubner, Y., Multhoff, G., Sauer, R., Fietkau, R., and Gaipl, U. S. (2011). Radiation combined with hyperthermia induces HSP70-dependent maturation of dendritic cells and release of pro-inflammatory cytokines by dendritic cells and macrophages. Radiother. Oncol. 101, 109-115.
119. Schildkopf, P., Holmer, R., Sieber, R., Ott, O. J., Janko, C., Mantel, F., Frey, B., Fietkau, R., and Gaipl, U. S. (2009). Hyperthermia in combination with X-irradiation induces inflammatory forms of cell death. Autoimmunity 42, 311-313.
120. Schreibelt, G., Klinkenberg, L. J., Cruz, L. J., Tacken, P. J., Tel, J., Kreutz, M., Adema, G. J., Brown, G. D., Figdor, C. G., and De Vries, I. J. (2012). The C-type lectin receptor CLEC9A mediates antigen uptake and (cross-)presentation by human blood BDCA3+ myeloid dendritic cells. Blood 119, 2284-2292.
121. Scott, R. S., Mcmahon, E. J., Pop, S. M., Reap, E. A., Caricchio, R., Cohen, P. L., Earp, H. S., and Matsushima, G. K. (2001). Phagocytosis and clearance of apoptotic cells is mediated by MER. Nature 411, 207-211.
122. Segundo, C., Medina, F., Rodriguez, C., Martinez-Palencia, R., Leyva-Cobian, F., and Brieva, J. A. (1999). Surface molecule loss and bleb formation by human germinal center B cells undergoing apoptosis: role of apoptotic blebs in monocyte chemotaxis. Blood 94, 1012-1020.
123. Sengupta, S., and Harris, C. C. (2005). p53: traffic cop at the crossroads of DNA repair and recombination. Nat. Rev. Mol. Cell Biol. 6, 44-55.
124. Shi, Y., Mucsi, A. D., and Ng, G. (2010). Monosodium urate crystals in inflammation and immunity. Immunol. Rev. 233, 203-217.
125. Shichita, T., Hasegawa, E., Kimura, A., Morita, R., Sakaguchi, R., Takada, I., Sekiya, T., Ooboshi, H., Kitazono, T., Yanagawa, T., Ishii, T., Takahashi, H., Mori, S., Nishibori, M., Kuroda, K., Akira, S., Miyake, K., and Yoshimura, A. (2012). Peroxiredoxin family proteins are key initiators of post-ischemic inflammation in the brain. Nat. Med. 18, 911-917.
126. Shiloh, Y. (2006). The ATM-mediated DNA-damage response: taking shape. Trends Biochem. Sci. 31, 402-410.
127. Silva, M. T. (2010). Secondary necrosis: the natural outcome of the complete apoptotic program. FEBS Lett. 584, 4491-4499.
128. Smith, J., Tho, L. M., Xu, N., and Gillespie, D. A. (2010). The ATM-Chk2 and ATR-Chk1 pathways in DNA damage signaling and cancer. Adv. Cancer Res. 108, 73-112.
129. Stangl, S., Gehrmann, M., Riegger, J., Kuhs, K., Riederer, I., Sievert, W., Hube, K., Mocikat, R., Dressel, R., Kremmer, E., Pockley, A. G., Friedrich, L., Vigh, L., Skerra, A., and Multhoff, G. (2011a). Targeting membrane heat-shock protein 70 (Hsp70) on tumors by cmHsp70.1 antibody. Proc. Natl. Acad. Sci. U.S.A. 108, 733-738.
130. Stangl, S., Themelis, G., Friedrich, L., Ntziachristos, V., Sarantopoulos, A., Molls, M., Skerra, A., and Multhoff, G. (2011b). Detection of irradiation-induced, membrane heat shock protein 70 (Hsp70) in mouse tumors using Hsp70 Fab fragment. Radiother. Oncol. 99, 313-316.
131. Steinman, R. M. (2007). Dendritic cells: understanding immunogenicity. Eur. J. Immunol. 37(Suppl. 1), S53-S60.
132. Stuart, L. M., Lucas, M., Simpson, C., Lamb, J., Savill, J., and Lacy-Hulbert, A. (2002). Inhibitory effects of apoptotic cell ingestion upon endotoxin-driven myeloid dendritic cell maturation. J. Immunol. 168, 1627-1635.
133. Tang, D., Kang, R., Cheh, C. W., Livesey, K. M., Liang, X., Schapiro, N. E., Benschop, R., Sparvero, L. J., Amoscato, A. A., Tracey, K. J., Zeh, H. J., and Lotze, M. T. (2010a). HMGB1 release and redox regulates autophagy and apoptosis in cancer cells. Oncogene 29, 5299-5310.
134. Tang, D., Kang, R., Livesey, K. M., Cheh, C. W., Farkas, A., Loughran, P., Hoppe, G., Bianchi, M. E., Tracey, K. J., Zeh, H. J. III, and Lotze, M. T. (2010b). Endogenous HMGB1 regulates autophagy. J. Cell Biol. 190, 881-892.
135. Taylor, R. C., Cullen, S. P., and Martin, S. J. (2008). Apoptosis: controlled demolition at the cellular level. Nat. Rev. Mol. Cell Biol. 9, 231-241.
136. Torr, E. E., Gardner, D. H., Thomas, L., Goodall, D. M., Bielemeier, A., Willetts, R., Griffiths, H. R., Marshall, L. J., and Devitt, A. (2012). Apoptotic cell-derived ICAM-3 promotes both macrophage chemoattraction to and tethering of apoptotic cells. Cell Death Differ. 19, 671-679.
137. Truman, L. A., Ford, C. A., Pasikowska, M., Pound, J. D., Wilkinson, S. J., Dumitriu, I. E., Melville, L., Melrose, L. A., Ogden, C. A., Nibbs, R., Graham, G., Combadiere, C., and Gregory, C. D. (2008). CX3CL1/fractalkine is released from apoptotic lymphocytes to stimulate macrophage chemotaxis. Blood 112, 5026-5036.
138. Tsan, M. F., and Gao, B. (2009). Heat shock proteins and immune system. J. Leukoc. Biol. 85, 905-910.
139. Urbonaviciute, V., Furnrohr, B. G., Meister, S., Munoz, L., Heyder, P., De Marchis, F., Bianchi, M. E., Kirschning, C., Wagner, H., Manfredi, A. A., Kalden, J. R., Schett, G., Rovere-Querini, P., Herrmann, M., and Voll, R. E. (2008). Induction of inflammatory and immune responses by HMGB1-nucleosome complexes: implications for the pathogenesis of SLE. J. Exp. Med. 205, 3007-3018.
140. Vandenabeele, P., Galluzzi, L., Vanden Berghe, T., and Kroemer, G. (2010). Molecular mechanisms of necroptosis: an ordered cellular explosion. Nat. Rev. Mol. Cell Biol. 11, 700-714.
141. Vanlangenakker, N., Vanden Berghe, T., and Vandenabeele, P. (2012). Many stimuli pull the necrotic trigger, an overview. Cell Death Differ. 19, 75-86.
142. Voll, R. E., Herrmann, M., Roth, E. A., Stach, C., Kalden, J. R., and Girkontaite, I. (1997). Immunosuppressive effects of apoptotic cells. Nature 390, 350-351.
143. Wagner, B. J., Lindau, D., Ripper, D., Stierhof, Y. D., Glatzle, J., Witte, M., Beck, H., Keppeler, H., Lauber, K., Rammensee, H. G., and Konigsrainer, A. (2011). Phagocytosis of dying tumor cells by human peritoneal mesothelial cells. J. Cell Sci. 124, 1644-1654.
144. Wakatsuki, M., Ohno, T., Iwakawa, M., Ishikawa, H., Noda, S., Ohta, T., Kato, S., Tsujii, H., Imai, T., and Nakano, T. (2008). p73 protein expression correlates with radiation-induced apoptosis in the lack of p53 response to radiation therapy for cervical cancer. Int. J. Radiat. Oncol. Biol. Phys. 70, 1189-1194.
145. Wu, Y., Singh, S., Georgescu, M. M., and Birge, R. B. (2005). A role for Mer tyrosine kinase in alphavbeta5 integrin-mediated phagocytosis of apoptotic cells. J. Cell Sci. 118, 539-553.
146. Xiong, W., Chen, Y., Wang, H., Wu, H., Lu, Q., and Han, D. (2008). Gas6 and the Tyro 3 receptor tyrosine kinase subfamily regulate the phagocytic function of Sertoli cells. Reproduction 135, 77-87.
147. Xue, W., Zender, L., Miething, C., Dickins, R. A., Hernando, E., Krizhanovsky, V., Cordon-Cardo, C., and Lowe, S. W. (2007). Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 445, 656-660.
148. Youle, R. J., and Strasser, A. (2008). The BCL-2 protein family: opposing activities that mediate cell death. Nat. Rev. Mol. Cell Biol. 9, 47-59.
149. Zelenay, S., Keller, A. M., Whitney, P. G., Schraml, B. U., Deddouche, S., Rogers, N. C., Schulz, O., Sancho, D., and Reis, E. S. C. (2012). The dendritic cell receptor DNGR-1 controls endocytic handling of necrotic cell antigens to favor cross-priming of CTLs in virus-infected mice. J. Clin. Invest. 122, 1615-1627.
150. Zhang, J. G., Czabotar, P. E., Policheni, A. N., Caminschi, I., Wan, S. S., Kitsoulis, S., Tullett, K. M., Robin, A. Y., Brammananth, R., Van Delft, M. F., Lu, J., O'Reilly, L. A., Josefsson, E. C., Kile, B. T., Chin, W. J., Mintern, J. D., Olshina, M. A., Wong, W., Baum, J., Wright, M. D., Huang, D. C., Mohandas, N., Coppel, R. L., Colman, P. M., Nicola, N. A., Shortman, K., and Lahoud, M. H. (2012). The dendritic cell receptor Clec9A binds damaged cells via exposed actin filaments. Immunity 36, 646-657.