Intratumoral delivery of immunotherapy - Act locally, think globally

Journal of Immunology

Volumn 198, Issue 1, 2017, Pages 31-39

  Aznar, M Angela ^a   Tinari, Nicola ^b   Rullán, Antonio J ^c   Sánchez Paulete, Alfonso R ^a   Rodriguez Ruiz, María E ^a,d   Melero, Ignacio ^a,d  

^a UNIVERSITY OF NAVARRA   (Spain)

^b UNIVERSITY OF CHIETI   (Italy)

^c CATALAN INSTITUTE OF ONCOLOGY   (Spain)

^d UNIVERSITY CLINIC OF NAVARRA   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

MONOCLONAL ANTIBODY; PATHOGEN ASSOCIATED MOLECULAR PATTERN; TUMOR ANTIGEN; ANTINEOPLASTIC AGENT;

CANCER GENE THERAPY; CANCER IMMUNOTHERAPY; CANCER RADIOTHERAPY; CELL THERAPY; HUMAN; IMMUNOCOMPETENT CELL; INTRATUMORAL DRUG ADMINISTRATION; NONHUMAN; ONCOLYTIC VIROTHERAPY; PRIORITY JOURNAL; REVIEW; ANIMAL; IMMUNOLOGY; IMMUNOTHERAPY; NEOPLASMS; PROCEDURES;

ANIMALS; ANTINEOPLASTIC AGENTS; HUMANS; IMMUNOTHERAPY; NEOPLASMS;

EID: 85007010443     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1601145     Document Type: Review

References (142)

1. Coley, W. B. 1906. Late results of the treatment of inoperable sarcoma by the mixed toxins of erysipelas and bacillus prodigiosus. Am. J. Med. Sci. 131: 375-430.
2. Coley, W. B. 1910. The treatment of inoperable sarcoma by bacterial toxins (the mixed toxins of the Streptococcus erysipelas and the Bacillus prodigiosus). Proc. R. Soc. Med. 3(Surg Sect): 1-48.
3. Han, R. F., and J. G. Pan. 2006. Can intravesical bacillus Calmette-Guérin reduce recurrence in patients with superficial bladder cancer? A meta-analysis of randomized trials. Urology 67: 1216-1223.
4. Janeway Jr., C. A. 1992. The immune system evolved to discriminate infectious nonself from noninfectious self. Immunol. Today 13: 11-16.
5. Matzinger, P. 2007. Friendly and dangerous signals: is the tissue in control? Nat. Immunol. 8: 11-13.
6. Hammerich, L., A. Binder, and J. D. Brody. 2015. In situ vaccination: cancer immunotherapy both personalized and off-the-shelf. Mol. Oncol. 9: 1966-1981.
7. Marabelle, A., H. Kohrt, C. Caux, and R. Levy. 2014. Intratumoral immunization: a new paradigm for cancer therapy. Clin. Cancer Res. 20: 1747-1756.
8. Kaminski, J. M., E. Shinohara, J. B. Summers, K. J. Niermann, A. Morimoto, and J. Brousal. 2005. The controversial abscopal effect. Cancer Treat. Rev. 31: 159-172.
9. Steinman, R. M. 2012. Decisions about dendritic cells: past, present, and future. Annu. Rev. Immunol. 30: 1-22.
10. Joffre, O. P., E. Segura, A. Savina, and S. Amigorena. 2012. Cross-presentation by dendritic cells. Nat. Rev. Immunol. 12: 557-569.
11. Inaba, K., S. Turley, F. Yamaide, T. Iyoda, K. Mahnke, M. Inaba, M. Pack, M. Subklewe, B. Sauter, D. Sheff, et al. 1998. Efficient presentation of phagocytosed cellular fragments on the major histocompatibility complex class II products of dendritic cells. J. Exp. Med. 188: 2163-2173.
12. Broz, M. L., M. Binnewies, B. Boldajipour, A. E. Nelson, J. L. Pollack, D. J. Erle, A. Barczak, M. D. Rosenblum, A. Daud, D. L. Barber, et al. 2014. Dissecting the tumor myeloid compartment reveals rare activating antigen-presenting cells critical for T cell immunity. Cancer Cell 26: 638-652.
13. Hildner, K., B. T. Edelson, W. E. Purtha, M. Diamond, H. Matsushita, M. Kohyama, B. Calderon, B. U. Schraml, E. R. Unanue, M. S. Diamond, et al. 2008. Batf3 deficiency reveals a critical role for CD8alpha+ dendritic cells in cytotoxic T cell immunity. Science 322: 1097-1100.
14. Schraml, B. U., and C. Reis e Sousa. 2015. Defining dendritic cells. Curr. Opin. Immunol. 32: 13-20.
15. Poulin, L. F., M. Salio, E. Griessinger, F. Anjos-Afonso, L. Craciun, J. L. Chen, A. M. Keller, O. Joffre, S. Zelenay, E. Nye, et al. 2010. Characterization of human DNGR-1+ BDCA3+ leukocytes as putative equivalents of mouse CD8alpha+ dendritic cells. J. Exp. Med. 207: 1261-1271.
16. Jongbloed, S. L., A. J. Kassianos, K. J. McDonald, G. J. Clark, X. Ju, C. E. Angel, C. J. Chen, P. R. Dunbar, R. B. Wadley, V. Jeet, et al. 2010. Human CD141+ (BDCA-3)+ dendritic cells (DCs) represent a unique myeloid DC subset that cross-presents necrotic cell antigens. J. Exp. Med. 207: 1247-1260.
17. Zitvogel, L., and G. Kroemer. 2014. CD103+ dendritic cells producing interleukin-12 in anticancer immunosurveillance. Cancer Cell 26: 591-593.
18. Martínez-López, M., S. Iborra, R. Conde-Garrosa, and D. Sancho. 2015. Batf3-dependent CD103+ dendritic cells are major producers of IL-12 that drive local Th1 immunity against Leishmania major infection in mice. Eur. J. Immunol. 45: 119-129.
19. Ghiringhelli, F., P. E. Puig, S. Roux, A. Parcellier, E. Schmitt, E. Solary, G. Kroemer, F. Martin, B. Chauffert, and L. Zitvogel. 2005. Tumor cells convert immature myeloid dendritic cells into TGF-beta-secreting cells inducing CD4 +CD25+ regulatory T cell proliferation. J. Exp. Med. 202: 919-929.
20. Herber, D. L., W. Cao, Y. Nefedova, S. V. Novitskiy, S. Nagaraj, V. A. Tyurin, A. Corzo, H. I. Cho, E. Celis, B. Lennox, et al. 2010. Lipid accumulation and dendritic cell dysfunction in cancer. Nat. Med. 16: 880-886.
21. Díaz-Valdés, N., L. Manterola, V. Belsúe, J. I. Riezu-Boj, E. Larrea, I. Echeverria, D. Llópiz, J. López-Sagaseta, H. Lerat, J. M. Pawlotsky, et al. 2011. Improved dendritic cell-based immunization against hepatitis C virus using peptide inhibitors of interleukin 10. Hepatology 53: 23-31.
22. Ruffell, B., D. Chang-Strachan, V. Chan, A. Rosenbusch, C. M. Ho, N. Pryer, D. Daniel, E. S. Hwang, H. S. Rugo, and L. M. Coussens. 2014. Macrophage IL-10 blocks CD8+ T cell-dependent responses to chemotherapy by suppressing IL-12 expression in intratumoral dendritic cells. Cancer Cell 26: 623-637.
23. Salmon, H., J. Idoyaga, A. Rahman, M. Leboeuf, R. Remark, S. Jordan, M. Casanova-Acebes, M. Khudoynazarova, J. Agudo, N. Tung, et al. 2016. Expansion and activation of CD103(+) dendritic cell progenitors at the tumor site enhances tumor responses to therapeutic PD-L1 and BRAF inhibition. Immunity 44: 924-938.
24. Sánchez-Paulete, A. R., F. J. Cueto, M. Martínez-López, S. Labiano, A. Morales-Kastresana, M. E. Rodríguez-Ruiz, M. Jure-Kunkel, A. Azpilikueta, M. A. Aznar, J. I. Quetglas, et al. 2016. Cancer immunotherapy with immunomodulatory anti-CD137 and anti-PD-1 monoclonal antibodies requires BATF3-dependent dendritic cells. Cancer Discov. 6: 71-79.
25. Sistigu, A., T. Yamazaki, E. Vacchelli, K. Chaba, D. P. Enot, J. Adam, I. Vitale, A. Goubar, E. E. Baracco, C. Remédios, et al. 2014. Cancer cell-autonomous contribution of type I interferon signaling to the efficacy of chemotherapy. Nat. Med. 20: 1301-1309.
26. Le Bon, A., N. Etchart, C. Rossmann, M. Ashton, S. Hou, D. Gewert, P. Borrow, and D. F. Tough. 2003. Cross-priming of CD8+ T cells stimulated by virus-induced type I interferon. Nat. Immunol. 4: 1009-1015.
27. Kroemer, G., L. Galluzzi, O. Kepp, and L. Zitvogel. 2013. Immunogenic cell death in cancer therapy. Annu. Rev. Immunol. 31: 51-72.
28. Schiavoni, G., A. Sistigu, M. Valentini, F. Mattei, P. Sestili, F. Spadaro, M. Sanchez, S. Lorenzi, M. T. D'Urso, F. Belardelli, et al. 2011. Cyclophosphamide synergizes with type I interferons through systemic dendritic cell reactivation and induction of immunogenic tumor apoptosis. Cancer Res. 71: 768-778.
29. Kumar, H., T. Kawai, and S. Akira. 2011. Pathogen recognition by the innate immune system. Int. Rev. Immunol. 30: 16-34.
30. Apetoh, L., F. Ghiringhelli, A. Tesniere, A. Criollo, C. Ortiz, R. Lidereau, C. Mariette, N. Chaput, J. P. Mira, S. Delaloge, et al. 2007. The interaction between HMGB1 and TLR4 dictates the outcome of anticancer chemotherapy and radiotherapy. Immunol. Rev. 220: 47-59.
31. Lasarte, J. J., N. Casares, M. Gorraiz, S. Hervás-Stubbs, L. Arribillaga, C. Mansilla, M. Durantez, D. Llopiz, P. Sarobe, F. Borrás-Cuesta, et al. 2007. The extra domain A from fibronectin targets antigens to TLR4-expressing cells and induces cytotoxic T cell responses in vivo. J. Immunol. 178: 748-756.
32. Chicoine, M. R., E. K. Won, and M. C. Zahner. 2001. Intratumoral injection of lipopolysaccharide causes regression of subcutaneously implanted mouse glioblastoma multiforme. Neurosurgery 48: 607-614; discussion 614-605. doi:10.1097/00006123-200103000-00032.
33. Van De Voort, T. J., M. A. Felder, R. K. Yang, P. M. Sondel, and A. L. Rakhmilevich. 2013. Intratumoral delivery of low doses of anti-CD40 mAb combined with monophosphoryl lipid A induces local and systemic antitumor effects in immunocompetent and T cell-deficient mice. J. Immunother. 36: 29-40.
34. Apetoh, L., F. Ghiringhelli, A. Tesniere, M. Obeid, C. Ortiz, A. Criollo, G. Mignot, M. C. Maiuri, E. Ullrich, P. Saulnier, et al. 2007. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat. Med. 13: 1050-1059.
35. Weide, B., T. K. Eigentler, A. Pflugfelder, H. Zelba, A. Martens, G. Pawelec, L. Giovannoni, P. A. Ruffini, G. Elia, D. Neri, et al. 2014. Intralesional treatment of stage III metastatic melanoma patients with L19-IL2 results in sustained clinical and systemic immunologic responses. Cancer Immunol. Res. 2: 668-678.
36. Bauer, S., C. J. Kirschning, H. Häcker, V. Redecke, S. Hausmann, S. Akira, H. Wagner, and G. B. Lipford. 2001. Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition. Proc. Natl. Acad. Sci. USA 98: 9237-9242.
37. Houot, R., and R. Levy. 2009. T-cell modulation combined with intratumoral CpG cures lymphoma in a mouse model without the need for chemotherapy. Blood 113: 3546-3552.
38. Li, J., W. Song, D. K. Czerwinski, B. Varghese, S. Uematsu, S. Akira, A. M. Krieg, and R. Levy. 2007. Lymphoma immunotherapy with CpG oligodeoxynucleotides requires TLR9 either in the host or in the tumor itself. J. Immunol. 179: 2493-2500.
39. Meng, Y., A. F. Carpentier, L. Chen, G. Boisserie, J. M. Simon, J. J. Mazeron, and J. Y. Delattre. 2005. Successful combination of local CpG-ODN and radiotherapy in malignant glioma. Int. J. Cancer 116: 992-997.
40. Brody, J. D., W. Z. Ai, D. K. Czerwinski, J. A. Torchia, M. Levy, R. H. Advani, Y. H. Kim, R. T. Hoppe, S. J. Knox, L. K. Shin, et al. 2010. In situ vaccination with a TLR9 agonist induces systemic lymphoma regression: a phase I/II study. J. Clin. Oncol. 28: 4324-4332.
41. Daud, A. I., R. C. DeConti, S. Andrews, P. Urbas, A. I. Riker, V. K. Sondak, P. N. Munster, D. M. Sullivan, K. E. Ugen, J. L. Messina, and R. Heller. 2008. Phase I trial of interleukin-12 plasmid electroporation in patients with metastatic melanoma. J. Clin. Oncol. 26: 5896-5903.
42. Rehwinkel, J., and C. Reis e Sousa. 2010. RIGorous detection: exposing virus through RNA sensing. Science 327: 284-286.
43. Alexopoulou, L., A. C. Holt, R. Medzhitov, and R. A. Flavell. 2001. Recognition of double-stranded RNA and activation of NF-kappaB by toll-like receptor 3. Nature 413: 732-738.
44. Amos, S. M., H. J. Pegram, J. A. Westwood, L. B. John, C. Devaud, C. J. Clarke, N. P. Restifo, M. J. Smyth, P. K. Darcy, and M. H. Kershaw. 2011. Adoptive immunotherapy combined with intratumoral TLR agonist delivery eradicates established melanoma in mice. Cancer Immunol. Immunother. 60: 671-683.
45. Bald, T., J. Landsberg, D. Lopez-Ramos, M. Renn, N. Glodde, P. Jansen, E. Gaffal, J. Steitz, R. Tolba, U. Kalinke, et al. 2014. Immune cell-poor melanomas benefit from PD-1 blockade after targeted type I IFN activation. Cancer Discov. 4: 674-687.
46. Salazar, A. M., R. B. Erlich, A. Mark, N. Bhardwaj, and R. B. Herberman. 2014. Therapeutic in situ autovaccination against solid cancers with intratumoral poly-ICLC: case report, hypothesis, and clinical trial. Cancer Immunol. Res. 2: 720-724.
47. Tormo, D., A. Checinska, D. Alonso-Curbelo, E. Pérez-Guijarro, E. Cañón, E. Riveiro-Falkenbach, T. G. Calvo, L. Larribere, D. Megías, F. Mulero, et al. 2009. Targeted activation of innate immunity for therapeutic induction of autophagy and apoptosis in melanoma cells. Cancer Cell 16: 103-114.
48. Jelinek, I., J. N. Leonard, G. E. Price, K. N. Brown, A. Meyer-Manlapat, P. K. Goldsmith, Y. Wang, D. Venzon, S. L. Epstein, and D. M. Segal. 2011. TLR3-specific double-stranded RNA oligonucleotide adjuvants induce dendritic cell cross-presentation, CTL responses, and antiviral protection. J. Immunol. 186:2422-2429.
49. Sidky, Y. A., E. C. Borden, C. E. Weeks, M. J. Reiter, J. F. Hatcher, and G. T. Bryan. 1992. Inhibition of murine tumor growth by an interferon-inducing imidazoquinolinamine. Cancer Res. 52: 3528-3533.
50. Ahonen, C. L., S. J. Gibson, R. M. Smith, L. K. Pederson, J. M. Lindh, M. A. Tomai, and J. P. Vasilakos. 1999. Dendritic cell maturation and subsequent enhanced T cell stimulation induced with the novel synthetic immune response modifier R-848. Cell. Immunol. 197: 62-72.
51. Smyth, E. C., M. Flavin, M. P. Pulitzer, G. J. Gardner, P. D. Costantino, D. S. Chi, K. Bogatch, P. B. Chapman, J. D. Wolchok, G. K. Schwartz, and R. D. Carvajal. 2011. Treatment of locally recurrent mucosal melanoma with topical imiquimod. J. Clin. Oncol. 29: e809-e811.
52. Redondo, P., J. del Olmo, A. López-Diaz de Cerio, S. Inoges, M. Marquina, I. Melero, and M. Bendandi. 2007. Imiquimod enhances the systemic immunity attained by local cryosurgery destruction of melanoma lesions. J. Invest. Dermatol. 127: 1673-1680.
53. Dewan, M. Z., C. Vanpouille-Box, N. Kawashima, S. DiNapoli, J. S. Babb, S. C. Formenti, S. Adams, and S. Demaria. 2012. Synergy of topical toll-like receptor 7 agonist with radiation and low-dose cyclophosphamide in a mouse model of cutaneous breast cancer. Clin. Cancer Res. 18: 6668-6678.
54. Adams, S., L. Kozhaya, F. Martiniuk, T. C. Meng, L. Chiriboga, L. Liebes, T. Hochman, N. Shuman, D. Axelrod, J. Speyer, et al. 2012. Topical TLR7 agonist imiquimod can induce immune-mediated rejection of skin metastases in patients with breast cancer. Clin. Cancer Res. 18: 6748-6757.
55. Corrales, L., L. H. Glickman, S. M. McWhirter, D. B. Kanne, K. E. Sivick, G. E. Katibah, S. R. Woo, E. Lemmens, T. Banda, J. J. Leong, et al. 2015. Direct activation of STING in the tumor microenvironment leads to potent and systemic tumor regression and immunity. Cell Rep. 11: 1018-1030.
56. Ablasser, A., M. Goldeck, T. Cavlar, T. Deimling, G. Witte, I. Röhl, K. P. Hopfner, J. Ludwig, and V. Hornung. 2013. cGAS produces a 2′-5′-linked cyclic dinucleotide second messenger that activates STING. Nature 498: 380-384.
57. Zhang, X., H. Shi, J. Wu, X. Zhang, L. Sun, C. Chen, and Z. J. Chen. 2013. Cyclic GMP-AMP containing mixed phosphodiester linkages is an endogenous high-affinity ligand for STING. Mol. Cell 51: 226-235.
58. Deng, L., H. Liang, M. Xu, X. Yang, B. Burnette, A. Arina, X. D. Li, H. Mauceri, M. Beckett, T. Darga, et al. 2014. STING-dependent cytosolic DNA sensing promotes radiation-induced type I interferon-dependent antitumor immunity in immunogenic tumors. Immunity 41: 843-852.
59. Woo, S. R., M. B. Fuertes, L. Corrales, S. Spranger, M. J. Furdyna, M. Y. Leung, R. Duggan, Y. Wang, G. N. Barber, K. A. Fitzgerald, et al. 2014. STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors. [Published erratum appears in 2015 Immunity 42: 199.] Immunity 41: 830-842.
60. Lichty, B. D., C. J. Breitbach, D. F. Stojdl, and J. C. Bell. 2014. Going viral with cancer immunotherapy. Nat. Rev. Cancer 14: 559-567.
61. Prestwich, R. J., K. J. Harrington, H. S. Pandha, R. G. Vile, A. A. Melcher, and F. Errington. 2008. Oncolytic viruses: a novel form of immunotherapy. Expert Rev. Anticancer Ther. 8: 1581-1588.
62. Smerdou, C., C. Ochoa, J. I. Quetglas, A. Fontanellas, G. Gonzalez-Aseguinolaza, R. G. Vile, and I. Melero. 2010. Immunology and gene therapy: shoulder to shoulder into the fray. Mol. Ther. 18: 456-459.
63. Goins, W. F., S. Huang, J. B. Cohen, and J. C. Glorioso. 2014. Engineering HSV-1 vectors for gene therapy. Methods Mol. Biol. 1144: 63-79.
64. Kim, J. H., J. Y. Oh, B. H. Park, D. E. Lee, J. S. Kim, H. E. Park, M. S. Roh, J. E. Je, J. H. Yoon, S. H. Thorne, D. Kirn, and T. H. Hwang. 2006. Systemic armed oncolytic and immunologic therapy for cancer with JX-594, a targeted poxvirus expressing GM-CSF. Mol. Ther. 14: 361-370.
65. Rodriguez-Madoz, J. R., J. Prieto, and C. Smerdou. 2005. Semliki forest virus vectors engineered to express higher IL-12 levels induce efficient elimination of murine colon adenocarcinomas. Mol. Ther. 12: 153-163.
66. Sangro, B., G. Mazzolini, J. Ruiz, M. Herraiz, J. Quiroga, I. Herrero, A. Benito, J. Larrache, J. Pueyo, J. C. Subtil, et al. 2004. Phase I trial of intratumoral injection of an adenovirus encoding interleukin-12 for advanced digestive tumors. J. Clin. Oncol. 22: 1389-1397.
67. Agrawal, N., C. Bettegowda, I. Cheong, J. F. Geschwind, C. G. Drake, E. L. Hipkiss, M. Tatsumi, L. H. Dang, L. A. Diaz, Jr., M. Pomper, et al. 2004. Bacteriolytic therapy can generate a potent immune response against experimental tumors. Proc. Natl. Acad. Sci. USA 101: 15172-15177.
68. Barajas, M., G. Mazzolini, G. Genové, R. Bilbao, I. Narvaiza, V. Schmitz, B. Sangro, I. Melero, C. Qian, and J. Prieto. 2001. Gene therapy of orthotopic hepatocellular carcinoma in rats using adenovirus coding for interleukin 12. Hepatology 33: 52-61.
69. Quetglas, J. I., M. Ruiz-Guillen, A. Aranda, E. Casales, J. Bezunartea, and C. Smerdou. 2010. Alphavirus vectors for cancer therapy. Virus Res. 153: 179-196.
70. Ott, P. A., and F. S. Hodi. 2016. Talimogene laherparepvec for the treatment of advanced melanoma. Clin. Cancer Res. 22: 3127-3131.
71. Lorence, R. M., K. W. Reichard, B. B. Katubig, H. M. Reyes, A. Phuangsab, B. R. Mitchell, C. J. Cascino, R. J. Walter, and M. E. Peeples. 1994. Complete regression of human neuroblastoma xenografts in athymic mice after local Newcastle disease virus therapy. J. Natl. Cancer Inst. 86: 1228-1233.
72. Nistal-Villan, E., M. Bunuales, J. Poutou, M. Gonzalez-Aparicio, C. Bravo-Perez, J. I. Quetglas, B. Carte, G. Gonzalez-Aseguinolaza, J. Prieto, E. Larrea, and R. Hernandez-Alcoceba. 2015. Enhanced therapeutic effect using sequential administration of antigenically distinct oncolytic viruses expressing oncostatin M in a Syrian hamster orthotopic pancreatic cancer model. Mol. Cancer 14: 210.
73. Zamarin, D., R. B. Holmgaard, S. K. Subudhi, J. S. Park, M. Mansour, P. Palese, T. Merghoub, J. D. Wolchok, and J. P. Allison. 2014. Localized oncolytic virotherapy overcomes systemic tumor resistance to immune checkpoint blockade immunotherapy. Sci. Transl. Med. 6: 226ra32.
74. Lundstrom, K. 2009. Alphaviruses in gene therapy. Viruses 1: 13-25.
75. Melero, I., J. I. Quetglas, M. Reboredo, J. Dubrot, J. R. Rodriguez-Madoz, U. Mancheño, E. Casales, J. I. Riezu-Boj, M. Ruiz-Guillen, M. C. Ochoa, et al. 2015. Strict requirement for vector-induced type I interferon in efficacious antitumor responses to virally encoded IL-12. Cancer Res. 75: 497-507.
76. Andtbacka, R. H., H. L. Kaufman, F. Collichio, T. Amatruda, N. Senzer, J. Chesney, K. A. Delman, L. E. Spitler, I. Puzanov, S. S. Agarwala, et al. 2015. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J. Clin. Oncol. 33: 2780-2788.
77. Narvaiza, I., G. Mazzolini, M. Barajas, M. Duarte, M. Zaratiegui, C. Qian, I. Melero, and J. Prieto. 2000. Intratumoral coinjection of two adenoviruses, one encoding the chemokine IFN-gamma-inducible protein-10 and another encoding IL-12, results in marked antitumoral synergy. J. Immunol. 164: 3112-3122.
78. Park, B. H., T. Hwang, T. C. Liu, D. Y. Sze, J. S. Kim, H. C. Kwon, S. Y. Oh, S. Y. Han, J. H. Yoon, S. H. Hong, et al. 2008. Use of a targeted oncolytic poxvirus, JX-594, in patients with refractory primary or metastatic liver cancer: a phase I trial. Lancet Oncol. 9: 533-542.
79. Quetglas, J. I., S. Labiano, M. A. Aznar, E. Bolaños, A. Azpilikueta, I. Rodriguez, E. Casales, A. R. Sánchez-Paulete, V. Segura, C. Smerdou, and I. Melero. 2015. Virotherapy with a Semliki forest virus-based vector encoding IL12 synergizes with PD-1/PD-L1 blockade. Cancer Immunol. Res. 3: 449-454.
80. Quetglas, J. I., J. Dubrot, J. Bezunartea, M. F. Sanmamed, S. Hervas-Stubbs, C. Smerdou, and I. Melero. 2012. Immunotherapeutic synergy between anti-CD137 mAb and intratumoral administration of a cytopathic Semliki Forest virus encoding IL-12. Mol. Ther. 20: 1664-1675.
81. John, L. B., L. J. Howland, J. K. Flynn, A. C. West, C. Devaud, C. P. Duong, T. J. Stewart, J. A. Westwood, Z. S. Guo, D. L. Bartlett, et al. 2012. Oncolytic virus and anti-4-1BB combination therapy elicits strong antitumor immunity against established cancer. Cancer Res. 72: 1651-1660.
82. Puzanov, I., M. M. Milhem, D. Minor, O. Hamid, A. Li, L. Chen, M. Chastain, K. S. Gorski, A. Anderson, J. Chou, et al. 2016. Talimogene laherparepvec in combination with ipilimumab in previously untreated, unresectable stage IIIB-IV melanoma. J. Clin. Oncol. 34: 2619-2626.
83. Breitbach, C. J., A. Moon, J. Burke, T. H. Hwang, and D. H. Kirn. 2015. A phase 2, open-label, randomized study of Pexa-Vec (JX-594) administered by intratumoral injection in patients with unresectable primary hepatocellular carcinoma. Methods Mol. Biol. 1317: 343-357.
84. Cripe, T. P., M. C. Ngo, J. I. Geller, C. U. Louis, M. A. Currier, J. M. Racadio, A. J. Towbin, C. M. Rooney, A. Pelusio, A. Moon, et al. 2015. Phase 1 study of intratumoral Pexa-Vec (JX-594), an oncolytic and immunotherapeutic vaccinia virus, in pediatric cancer patients. Mol. Ther. 23: 602-608.
85. Huang, P. I., J. F. Chang, D. H. Kirn, and T. C. Liu. 2009. Targeted genetic and viral therapy for advanced head and neck cancers. Drug Discov. Today 14: 570-578.
86. Liu, T. C., S. H. Thorne, and D. H. Kirn. 2008. Oncolytic adenoviruses for cancer gene therapy. Methods Mol. Biol. 433: 243-258.
87. Huarte, E., E. Larrea, R. Hernandez-Alcoceba, C. Alfaro, O. Murillo, A. Arina, I. Tirapu, A. Azpilicueta, S. Hervas-Stubbs, S. Bortolanza, et al. 2006. Recombinant adenoviral vectors turn on the type I interferon system without inhibition of transgene expression and viral replication. Mol. Ther. 14: 129-138.
88. Kawai, T., and S. Akira. 2011. Toll-like receptors and their cross-talk with other innate receptors in infection and immunity. Immunity 34: 637-650.
89. Takeuchi, O., and S. Akira. 2008. MDA5/RIG-I and virus recognition. Curr. Opin. Immunol. 20: 17-22.
90. Sharma, P., and J. P. Allison. 2015. The future of immune checkpoint therapy. Science 348: 56-61.
91. Topalian, S. L., C. G. Drake, and D. M. Pardoll. 2015. Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell 27: 450-461.
92. Kohrt, H. E., P. C. Tumeh, D. Benson, N. Bhardwaj, J. Brody, S. Formenti, B. A. Fox, J. Galon, C. H. June, M. Kalos, et al; Cancer Immunotherapy Trials Network (CITN). 2016. Immunodynamics: a cancer immunotherapy trials network review of immune monitoring in immuno-oncology clinical trials. J. Immunother. Cancer 4: 15.
93. Das, R., R. Verma, M. Sznol, C. S. Boddupalli, S. N. Gettinger, H. Kluger, M. Callahan, J. D. Wolchok, R. Halaban, M. V. Dhodapkar, and K. M. Dhodapkar. 2015. Combination therapy with anti-CTLA-4 and anti-PD-1 leads to distinct immunologic changes in vivo. J. Immunol. 194: 950-959.
94. Melief, C. J. 2012. Selective activation of oxygen-deprived tumor-infiltrating lymphocytes through local intratumoral delivery of CD137 monoclonal antibodies. Cancer Discov. 2: 586-587.
95. Fransen, M. F., T. C. van der Sluis, F. Ossendorp, R. Arens, and C. J. Melief. 2013. Controlled local delivery of CTLA-4 blocking antibody induces CD8+ T cell-dependent tumor eradication and decreases risk of toxic side effects. Clin. Cancer Res. 19: 5381-5389.
96. Fransen, M. F., M. Sluijter, H. Morreau, R. Arens, and C. J. Melief. 2011. Local activation of CD8 T cells and systemic tumor eradication without toxicity via slow release and local delivery of agonistic CD40 antibody. Clin. Cancer Res. 17: 2270-2280.
97. Fransen, M. F., R. A. Cordfunke, M. Sluijter, M. J. van Steenbergen, J. W. Drijfhout, F. Ossendorp, W. E. Hennink, and C. J. Melief. 2014. Effectiveness of slow-release systems in CD40 agonistic antibody immunotherapy of cancer. Vaccine 32: 1654-1660.
98. Marabelle, A., H. Kohrt, and R. Levy. 2014. New insights into the mechanism of action of immune checkpoint antibodies. OncoImmunology 3: e954869.
99. Marabelle, A., H. Kohrt, I. Sagiv-Barfi, B. Ajami, R. C. Axtell, G. Zhou, R. Rajapaksa, M. R. Green, J. Torchia, J. Brody, et al. 2013. Depleting tumor-specific Tregs at a single site eradicates disseminated tumors. J. Clin. Invest. 123: 2447-2463.
100. Lehmann, S., R. Perera, H. P. Grimm, J. Sam, S. Colombetti, T. Fauti, L. Fahrni, T. Schaller, A. Freimoser-Grundschober, J. Zielonka, et al. 2016. In vivo imaging of the activity of CEA TCB, a novel T cell bispecific antibody, reveals specific tumor targeting and fast induction of T cell mediated tumor killing. Clin. Cancer Res. 22: 4417-4427.
101. Palazón, A., I. Martínez-Forero, A. Teijeira, A. Morales-Kastresana, C. Alfaro, M. F. Sanmamed, J. L. Perez-Gracia, I. Peñuelas, S. Hervás-Stubbs, A. Rouzaut, et al. 2012. The HIF-1α hypoxia response in tumor-infiltrating T lymphocytes induces functional CD137 (4-1BB) for immunotherapy. Cancer Discov. 2: 608-623.
102. Beatty, G. L., D. A. Torigian, E. G. Chiorean, B. Saboury, A. Brothers, A. Alavi, A. B. Troxel, W. Sun, U. R. Teitelbaum, R. H. Vonderheide, and P. J. O'Dwyer. 2013. A phase I study of an agonist CD40 monoclonal antibody (CP-870,893) in combination with gemcitabine in patients with advanced pancreatic ductal adenocarcinoma. Clin. Cancer Res. 19: 6286-6295.
103. Dubrot, J., F. Milheiro, C. Alfaro, A. Palazón, I. Martinez-Forero, J. L. Perez-Gracia, A. Morales-Kastresana, J. L. Romero-Trevejo, M. C. Ochoa, S. Hervás-Stubbs, et al. 2010. Treatment with anti-CD137 mAbs causes intense accumulations of liver T cells without selective antitumor immunotherapeutic effects in this organ. Cancer Immunol. Immunother. 59: 1223-1233.
104. Nowak, A. K., A. M. Cook, A. M. McDonnell, M. J. Millward, J. Creaney, R. J. Francis, A. Hasani, A. Segal, A. W. Musk, B. A. Turlach, M. J. McCoy, B. W. Robinson, and R. A. Lake. 2015. A phase 1b clinical trial of the CD40-activating antibody CP-870,893 in combination with cisplatin and pemetrexed in malignant pleural mesothelioma. Ann. Oncol. 26: 2483-2490.
105. Vonderheide, R. H., K. T. Flaherty, M. Khalil, M. S. Stumacher, D. L. Bajor, N. A. Hutnick, P. Sullivan, J. J. Mahany, M. Gallagher, A. Kramer, et al. 2007. Clinical activity and immune modulation in cancer patients treated with CP-870,893, a novel CD40 agonist monoclonal antibody. J. Clin. Oncol. 25: 876-883.
106. Bol, K. F., G. Schreibelt, W. R. Gerritsen, I. J. de Vries, and C. G. Figdor. 2016. Dendritic cell-based immunotherapy: state of the art and beyond. Clin. Cancer Res. 22: 1897-1906.
107. Alfaro, C., J. L. Perez-Gracia, N. Suarez, J. Rodriguez, M. Fernandez de Sanmamed, B. Sangro, S. Martin-Algarra, A. Calvo, M. Redrado, A. Agliano, et al. 2011. Pilot clinical trial of type 1 dendritic cells loaded with autologous tumor lysates combined with GM-CSF, pegylated IFN, and cyclophosphamide for metastatic cancer patients. J. Immunol. 187: 6130-6142.
108. Bedrosian, I., R. Mick, S. Xu, H. Nisenbaum, M. Faries, P. Zhang, P. A. Cohen, G. Koski, and B. J. Czerniecki. 2003. Intranodal administration of peptide-pulsed mature dendritic cell vaccines results in superior CD8+ T cell function in melanoma patients. J. Clin. Oncol. 21: 3826-3835.
109. Gilliet, M., M. Kleinhans, E. Lantelme, D. Schadendorf, G. Burg, and F. O. Nestle. 2003. Intranodal injection of semimature monocyte-derived dendritic cells induces T helper type 1 responses to protein neoantigen. Blood 102: 36-42.
110. Melero, I., M. Duarte, J. Ruiz, B. Sangro, J. Galofré, G. Mazzolini, M. Bustos, C. Qian, and J. Prieto. 1999. Intratumoral injection of bone-marrow derived dendritic cells engineered to produce interleukin-12 induces complete regression of established murine transplantable colon adenocarcinomas. Gene Ther. 6: 1779-1784.
111. Nishioka, Y., M. Hirao, P. D. Robbins, M. T. Lotze, and H. Tahara. 1999. Induction of systemic and therapeutic antitumor immunity using intratumoral injection of dendritic cells genetically modified to express interleukin 12. Cancer Res. 59: 4035-4041.
112. Van Lint, S., D. Renmans, K. Broos, L. Goethals, S. Maenhout, D. Benteyn, C. Goyvaerts, S. Du Four, K. Van der Jeught, L. Bialkowski, et al. 2016. Intratumoral delivery of TriMix mRNA results in T cell activation by cross-presenting dendritic cells. Cancer Immunol. Res. 4: 146-156.
113. Mazzolini, G., C. Alfaro, B. Sangro, E. Feijoó, J. Ruiz, A. Benito, I. Tirapu, A. Arina, J. Sola, M. Herraiz, et al. 2005. Intratumoral injection of dendritic cells engineered to secrete interleukin-12 by recombinant adenovirus in patients with metastatic gastrointestinal carcinomas. J. Clin. Oncol. 23: 999-1010.
114. Alfaro, C., N. Suárez, I. Martínez-Forero, A. Palazón, A. Rouzaut, S. Solano, E. Feijoo, A. Gúrpide, E. Bolaños, L. Erro, et al. 2011. Carcinoma-derived interleukin-8 disorients dendritic cell migration without impairing T cell stimulation. PLoS One 6: e17922.
115. Melero, I., A. Arina, O. Murillo, J. Dubrot, C. Alfaro, J. L. Perez-Gracia, M. Bendandi, and S. Hervas-Stubbs. 2006. Immunogenic cell death and cross-priming are reaching the clinical immunotherapy arena. Clin. Cancer Res. 12: 2385-2389.
116. Spranger, S., R. Bao, and T. F. Gajewski. 2015. Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity. Nature 523: 231-235.
117. Melero, I., R. G. Vile, and M. P. Colombo. 2000. Feeding dendritic cells with tumor antigens: self-service buffet or à la carte? Gene Ther. 7: 1167-1170.
118. Chi, K. H., S. J. Liu, C. P. Li, H. P. Kuo, Y. S. Wang, Y. Chao, and S. L. Hsieh. 2005. Combination of conformal radiotherapy and intratumoral injection of adoptive dendritic cell immunotherapy in refractory hepatoma. J. Immunother. 28: 129-135.
119. Breton, G., J. Lee, Y. J. Zhou, J. J. Schreiber, T. Keler, S. Puhr, N. Anandasabapathy, S. Schlesinger, M. Caskey, K. Liu, and M. C. Nussenzweig. 2015. Circulating precursors of human CD1c+ and CD141+ dendritic cells. J. Exp. Med. 212: 401-413.
120. Gorelik, L., and R. A. Flavell. 2002. Transforming growth factor-beta in T cell biology. Nat. Rev. Immunol. 2: 46-53.
121. Li, M. O., Y. Y. Wan, S. Sanjabi, A. K. Robertson, and R. A. Flavell. 2006. Transforming growth factor-beta regulation of immune responses. Annu. Rev. Immunol. 24: 99-146.
122. Maus, M. V., and C. H. June. 2016. Making better chimeric antigen receptors for adoptive T cell therapy. Clin. Cancer Res. 22: 1875-1884.
123. Rosenberg, S. A., and N. P. Restifo. 2015. Adoptive cell transfer as personalized immunotherapy for human cancer. Science 348: 62-68.
124. Melero, I., A. Rouzaut, G. T. Motz, and G. Coukos. 2014. T cell and NK cell infiltration into solid tumors: a key limiting factor for efficacious cancer immunotherapy. Cancer Discov. 4: 522-526.
125. Arina, A., O. Murillo, S. Hervás-Stubbs, A. Azpilikueta, J. Dubrot, I. Tirapu, E. Huarte, C. Alfaro, J. L. Pérez-Gracia, G. González-Aseguinolaza, et al. 2007. The combined actions of NK and T lymphocytes are necessary to reject an EGFP+ mesenchymal tumor through mechanisms dependent on NKG2D and IFN gamma. Int. J. Cancer 121: 1282-1295.
126. Golden, E. B., I. Pellicciotta, S. Demaria, M. H. Barcellos-Hoff, and S. C. Formenti. 2012. The convergence of radiation and immunogenic cell death signaling pathways. Front. Oncol. 2: 88.
127. Kepp, O., L. Senovilla, I. Vitale, E. Vacchelli, S. Adjemian, P. Agostinis, L. Apetoh, F. Aranda, V. Barnaba, N. Bloy, et al. 2014. Consensus guidelines for the detection of immunogenic cell death. OncoImmunology 3: e955691.
128. Antoniades, J., L. W. Brady, and D. A. Lightfoot. 1977. Lymphangiographic demonstration of the abscopal effect in patients with malignant lymphomas. Int. J. Radiat. Oncol. Biol. Phys. 2: 141-147.
129. Deng, L., H. Liang, B. Burnette, M. Beckett, T. Darga, R. R. Weichselbaum, and Y. X. Fu. 2014. Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice. J. Clin. Invest. 124: 687-695.
130. Ruocco, M. G., K. A. Pilones, N. Kawashima, M. Cammer, J. Huang, J. S. Babb, M. Liu, S. C. Formenti, M. L. Dustin, and S. Demaria. 2012. Suppressing T cell motility induced by anti-CTLA-4 monotherapy improves antitumor effects. J. Clin. Invest. 122: 3718-3730.
131. Twyman-Saint Victor, C., A. J. Rech, A. Maity, R. Rengan, K. E. Pauken, E. Stelekati, J. L. Benci, B. Xu, H. Dada, P. M. Odorizzi, et al. 2015. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature 520: 373-377.
132. Postow, M. A., M. K. Callahan, C. A. Barker, Y. Yamada, J. Yuan, S. Kitano, Z. Mu, T. Rasalan, M. Adamow, E. Ritter, et al. 2012. Immunologic correlates of the abscopal effect in a patient with melanoma. N. Engl. J. Med. 366: 925-931.
133. Shi, L., L. Chen, C. Wu, Y. Zhu, B. Xu, X. Zheng, M. Sun, W. Wen, X. Dai, M. Yang, Q. Lv, B. Lu, and J. Jiang. 2016. PD-1 blockade boosts radiofrequency ablation-elicited adaptive immune responses against tumor. Clin. Cancer Res. 22: 1173-1184.
134. Mozzillo, N., E. Simeone, L. Benedetto, M. Curvietto, D. Giannarelli, G. Gentilcore, R. Camerlingo, M. Capone, G. Madonna, L. Festino, et al. 2015. Assessing a novel immuno-oncology-based combination therapy: ipilimumab plus electrochemotherapy. OncoImmunology 4: e1008842.
135. Korangy, F., M. ElGindi, D. Pratt, D. Venzon, A. Duffy, O. Makarova-Rusher, S. Kerkar, D. Kleiner, B. Wood, and T. Greten. 2016. Tremelimimab activates CD4 and CD8+T cells in patients with hepatocellular carcinoma. Cancer Immunol. Res. 4. (1 Suppl):Abstract nr A195.
136. Barker, H. E., J. T. Paget, A. A. Khan, and K. J. Harrington. 2015. The tumour microenvironment after radiotherapy: mechanisms of resistance and recurrence. Nat. Rev. Cancer 15: 409-425.
137. + T cells is crucial to inhibit the growth of mucosal tumors. Sci. Transl. Med. 5: 172ra20.
138. Mikhak, Z., J. P. Strassner, and A. D. Luster. 2013. Lung dendritic cells imprint T cell lung homing and promote lung immunity through the chemokine receptor CCR4. J. Exp. Med. 210: 1855-1869.
139. Kaufman, H. L., T. Amatruda, T. Reid, R. Gonzalez, J. Glaspy, E. Whitman, K. Harrington, J. Nemunaitis, A. Zloza, M. Wolf, and N. N. Senzer. 2016. Systemic versus local responses in melanoma patients treated with talimogene laherparepvec from a multi-institutional phase II study. J. Immunother. Cancer 4: 12.
140. Melero, I., D. M. Berman, M. A. Aznar, A. J. Korman, J. L. Pérez Gracia, and J. Haanen. 2015. Evolving synergistic combinations of targeted immunotherapies to combat cancer. Nat. Rev. Cancer 15: 457-472.
141. Whiteside, T. L., S. Demaria, M. E. Rodriguez-Ruiz, H. M. Zarour, and I. Melero. 2016. Emerging opportunities and challenges in cancer immunotherapy. Clin. Cancer Res. 22: 1845-1855.
142. Berraondo, P., M. C. Ochoa, M. E. Rodriguez-Ruiz, L. Minute, J. J. Lasarte, and I. Melero. 2016. Immunostimulatory monoclonal antibodies and immunomodulation: harvesting the crop. Cancer Res. 76: 2863-2867.