The role of the immunosuppressive microenvironment in acute myeloid leukemia development and treatment

Expert Review of Hematology

Volumn 7, Issue 6, 2014, Pages 807-818

  Isidori, Alessandro ^a   Salvestrini, Valentina ^b   Ciciarello, Marilena ^b   Loscocco, Federica ^a   Visani, Giuseppe ^a   Parisi, Sarah ^b   Lecciso, Mariangela ^b   Ocadlikova, Darina ^b   Rossi, Lara ^b   Gabucci, Elisa ^a   Clissa, Cristina ^a   Curti, Antonio ^b  

^a AORMN   (Italy)

^b UNIVERSITY OF BOLOGNA   (Italy)

Author keywords

Acute myeloid leukemia; Immunotherapy; Microenvironment; Tolerogenic; Tumor immunity

Indexed keywords

ADENOSINE TRIPHOSPHATE; ARGININE; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; LENALIDOMIDE; NUCLEOTIDE; PROGRAMMED DEATH 1 LIGAND 1; PURINERGIC P2 RECEPTOR; PURINERGIC P2X7 RECEPTOR; TRYPTOPHAN;

ACUTE GRANULOCYTIC LEUKEMIA; ADAPTIVE IMMUNITY; ADOPTIVE IMMUNOTHERAPY; ALLOGENEIC STEM CELL TRANSPLANTATION; CANCER CELL; CANCER SURVIVAL; CANCER THERAPY; CATABOLISM; CELL COMMUNICATION; CELL DEATH; CELL MIGRATION; CLINICAL TRIAL (TOPIC); DISEASE COURSE; DRUG TARGETING; EXOSOME; HUMAN; IMMUNE SYSTEM; IMMUNOCOMPETENT CELL; IMMUNOGENICITY; IMMUNOLOGICAL TOLERANCE; IMMUNOTHERAPY; LEUKEMIA CELL; MESENCHYMAL STROMA CELL; PHASE 1 CLINICAL TRIAL (TOPIC); REGULATORY MECHANISM; REGULATORY T LYMPHOCYTE; REVIEW; SIGNAL TRANSDUCTION; STEM CELL TRANSPLANTATION; TUMOR IMMUNITY; TUMOR MICROENVIRONMENT; VACCINATION; ANIMAL; IMMUNITY; IMMUNOLOGY; LEUKEMIA, MYELOID, ACUTE; PATHOLOGY; PROCEDURES;

ANIMALS; HUMANS; IMMUNE TOLERANCE; IMMUNITY; IMMUNOTHERAPY; LEUKEMIA, MYELOID, ACUTE; STEM CELL TRANSPLANTATION; TUMOR MICROENVIRONMENT;

EID: 84911392660     PISSN: 17474086     EISSN: 17474094     Source Type: Journal    
DOI: 10.1586/17474086.2014.958464     Document Type: Review

References (113)

1. Isidori A, Venditti A, Maurillo L, et al. Alternative novel therapies for the treatment of elderly acute myeloid leukemia patients. Exp Rev Hematol 2013;6(6):767-84
2. Ayala F, Dewar R, Kieran M, Kalluri R Contribution of bone microenvironment to leukemogenesis and leukemia progression. Leukemia 2009;23:2233-41
3. Zeng Z, Shi YX, Samudio IJ, et al. Targeting the leukemia microenvironment by CXCR4 inhibition overcomes resistance to kinase inhibitors and chemotherapy in AML. Blood 2009;113:6215-24
4. Dunn GP, Bruce AT, Ikeda H, et al. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol 2002;3:991-8
5. Buggins AG, Milojkovic D, Arno MJ, et al. Microenvironment produced by acute myeloid leukemia cells prevents T cell activation and proliferation by inhibition of NF-kappaB, c-Myc, and pRb pathways. J Immunol 2001;167(10):6021-30
6. Orleans-Lindsay JK, Barber LD, Prentice HG, Lowdell MW. Acute myeloid leukaemia cells secrete a soluble factor that inhibits T and NK cell proliferation but not cytolytic function-implications for the adoptive immunotherapy of leukaemia. Clin Exp Immunol 2001;126(3):403-11
7. Le Dieu R, Taussig DC, Ramsay AG, et al. Peripheral blood T cells in acute myeloid leukemia (AML) patients at diagnosis have abnormal phenotype and genotype and form defective immune synapses with AML blasts. Blood 2009;114(18):3909-16
8. Ustun C, Miller JS, Munn DH, et al. Regulatory T cells in acute myelogenous leukemia: is it time for immunomodulation? Blood 2011;118(19):5084-95
9. Zhang L, Gajewski TF, Kline J. PD-1/PD-L1 interactions inhibit antitumor immune responses in a murine acute myeloid leukemia model. Blood 2009; 114(8):1545-52
10. Mellor AL, Munn DH. Tryptophan catabolism and T-cell tolerance: immunosuppression by starvation? Immunol Today 1999;20:469-73
11. Frumento G, Rotondo R, Tonetti M, et al. Tryptophan-derived catabolites are responsible for inhibition of T and natural killer cell proliferation induced by indoleamine 2, 3-dioxygenase. J Exp Med 2002;196:459-68
12. Grohmann U, Fallarino F, Puccetti P. Tolerance, DCs and tryptophan: much ado about IDO. Trends Immunol 2003;24: 242-8
13. Uyttenhove C, Pilotte L, Theate I, et al. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2, 3-dioxygenase. Nat Med 2003;9:1269-74
14. Munn DH, Mellor AL. IDO and tolerance to tumors. Trends Mol Med 2004;10:15-18
15. Platten M, Wick W, Van den Eynde BJ. Tryptophan catabolism in cancer: beyond IDO and tryptophan depletion. Cancer Res 2012;72(21):5435-40
16. Godin-Ethier J, Hanafi LA, Piccirillo CA, Lapointe R. Indoleamine 2, 3-dioxygenase expression in human cancers: clinical and immunologic perspectives. Clin Cancer Res 2011;17(22):6985-91
17. Curti A, Pandolfi S, Valzasina B, et al. Modulation of tryptophan catabolism by human leukemic cells results in the conversion of CD25-into CD25+ T regulatory cells. Blood 2007;109(7):2871-7
18. Curti A, Trabanelli S, Onofri C, et al. Indoleamine 2, 3-dioxygenase-expressing leukemic dendritic cells impair a leukemia-specific immune response by inducing potent T regulatory cells. Haematologica 2010;95(12):2022-30
19. Chamuleau ME, Van de Loosdrecht AA, Hess CJ, et al. High INDO (indoleamine 2, 3-dioxygenase) mRNA level in blasts of acute myeloid leukemic patients predicts poor clinical outcome. Haematologica 2008; 93(12):1894-8
20. Muller AJ, DuHadaway JB, Donover PS, et al. Inhibition of indoleamine 2, 3-dioxygenase, an immunoregulatory target of the cancer suppression gene Bin1, potentiates cancer chemotherapy. Nat Med 2005;11:312-19
21. Lob S, Konigsrainer A, Zieker D, et al. IDO1 and IDO2 are expressed in human tumors: levo-but not dextro-1-methyl tryptophan inhibits tryptophan catabolism. Cancer Immunol Immunother 2009;58: 153-7
22. Lob S, Konigsrainer A, Rammensee HG, et al. Inhibitors of indoleamine-2, 3-dioxygenase for cancer therapy: can we see the wood for the trees? Nat Rev Cancer 2009;9:445-52
23. Metz R, Duhadaway JB, Kamasani U, et al. Novel tryptophan catabolic enzyme IDO2 is the preferred biochemical target of the antitumor indoleamine 2, 3-dioxygenase inhibitory compound D-1-methyl-tryptophan. Cancer Res 2007;67:7082-7
24. Andersen MH. The targeting of immunosuppressive mechanisms in hematological malignancies. Leukemia. 2014. [Epub ahead of print]
25. Phase II INCB024360 study for patients with myelodysplastic syndromes (MDS). Available from: http://clinicaltrials.gov/show/NCT01822691
26. Gabrilovich DI, Ostrand-Rosenberg S, Bronte V. Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol 2012;12(4):253-68
27. Mussai F, De Santo C, Abu-Dayyeh I, et al. Acute myeloid leukemia creates an arginase-dependent immunosuppressive microenvironment. Blood 2013;122(5): 749-58
28. Riley JL. PD-1 signaling in primary T cells. Immunol Rev 2009;229(1):114-25
29. Duraiswamy J, Kaluza KM, Freeman GJ, Coukos G. Dual blockade of PD-1 and CTLA-4 combined with tumor vaccine effectively restores T-cell rejection function in tumors. Cancer Res 2013;73(12): 3591-603
30. John LB, Devaud C, Duong CP, et al. Anti-PD-1 antibody therapy potently enhances the eradication of established tumors by gene-modified T cells. Clin Cancer Res 2013;19(20):5636-46
31. Pilon-Thomas S, Mackay A, Vohra N, Mule JJ. Blockade of programmed death ligand 1 enhances the therapeutic efficacy of combination immunotherapy against melanoma. J Immunol 2010;184(7):3442-9
32. Yang H, Bueso-Ramos C, DiNardo C, et al. Expression of PD-L1, PD-L2, PD-1 and CTLA4 in myelodysplastic syndromes is enhanced by treatment with hypomethylating agents. Leukemia 2014; 28(6):1280-8
33. Corre J, Mahtouk K, Attal M, et al. Bone marrow mesenchymal stem cells are abnormal in multiple myeloma. Leukemia 2007;2:1079-88
34. Fibbe WE, Nauta AJ, Roelofs H. Modulation of immune responses by mesenchymal stem cells. Ann NY Acad Sci 2007;1106:272-8
35. Shi L, Chen S, Yang L, et al.1 and PD-L1 in T-cell immune suppression in patients with hematological malignancies. J Hematol Oncol 2013;6(1):74
36. Berger R, Rotem-Yehudar R, Slama G, et al. Phase I safety and pharmacokinetic study of CT-011, a humanized antibody interacting with PD-1, in patients with advanced hematologic malignancies. Clin Cancer Res 2008;14(10):3044-51
37. Blockade of PD-1 in conjunction with the dendritic Cell/AML vaccine following chemotherapy induced remission. Available from: http://clinicaltrials.gov/show/NCT01096602
38. Chambers CA, Kuhns MS, Egen JG, Allison JP. CTLA-4-mediated inhibition in regulation of T cell responses: mechanisms and manipulation in tumor immunotherapy. Annu Rev Immunol 2001;19:565-94
39. Prieto PA, Yang JC, Sherry RM, et al. CTLA-4 blockade with ipilimumab: long-term follow-up of 177 patients with metastatic melanoma. Clin Cancer Res 2012;18(7):2039-47
40. Brahmer JR Harnessing the immune system for the treatment of non-small-cell lung cancer. J Clin Oncol 2013;31(8):1021-8
41. Perez-Garćia A, Brunet S, Berlanga JJ, et al. Grupo cooperativo para el estudio y tratamiento de las leucemias agudas. CTLA-4 genotype and relapse incidence in patients with acute myeloid leukemia in first complete remission after induction chemotherapy. Leukemia 2009;23(3):486-91
42. Bashey A, Medina B, Corringham S, et al. CTLA4 blockade with ipilimumab to treat relapse of malignancy after allogeneic hematopoietic cell transplantation. Blood 2009; 113(7):1581-8
43. Ipilimumab in treating patients with relapsed hematologic malignancies after donor stem cell transplant. Available from: http://clinicaltrials.gov/show/NCT01822509
44. Ipilimumab after allogeneic stem cell transplant in treating patients with persistent or progressive cancer. Available from: http://clinicaltrials.gov/show/NCT00060372
45. Fevery S, Billiau AD, Sprangers B, et al. CTLA-4 blockade in murine bone marrow chimeras induces a host-derived antileukemic effect without graft-versus-host disease. Leukemia 2007;21:1451-9
46. Caplan AI. Mesenchymal stem cells. J Orthop Res 1991;9:641-50
47. Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999;284: 143-7
48. Zhang J, Niu C, Ye L, et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature 2003;425: 836-41
49. Wallace SR, Oken MM, Lunetta KL, et al. Abnormalities of bone marrow mesenchymal cells in multiple myeloma patients. Cancer 2001;91:1219-30
50. Arnulf B, Lecourt S, Soulier J, et al. Phenotypic and functional characterization of bone marrow mesenchymal stem cells derived from patients with multiple myeloma. Leukemia 2007;21:158-63
51. Conforti A, Biagini S, Del Bufalo F, et al. Biological, functional and genetic characterization of bone marrow-derived mesenchymal stromal cells from pediatric patients affected by acute lymphoblastic leukemia. PLoS One 2013;8(11):e76989
52. Blau O, Baldus CD, Hofmann WK, et al. Mesenchymal stroma cells of myelodysplastic syndrome and acute myeloid leukemia patients have distinct genetic abnormalities compared with leukemic blasts. Blood 2011;118(20): 5583-92
53. Raaijmakers MH, Mukherjee S, Guo S, et al. Bone progenitor dysfunction induces myelodysplasia and secondary leukemia. Nature 2010;464(7290):852-7
54. Flores-Figueroa E, Arana-Trejo RM, Gutierrez-Espindola G, et al. Mesenchymal stem cells in myelodysplastic syndromes: phenotypic and cytogenetic characterization. Leuk Res 2005;29:215-24
55. Blau O, Hofmann WK, Baldus CD, et al. Chromosomal aberrations in bone marrow mesenchymal stroma cells from patients with myelodysplastic syndrome and acute myeloblastic leukemia. Exp Hematol 2007;35:221-9
56. Sparrow RL, O'Flaherty E, Blanksby TM, et al. Perturbation in the ability of bone marrow stroma from patients with acute myeloid leukemia but not chronic myeloid leukemia to support normal early hematopoietic progenitor cells. Leuk Res 1997;21(1):29-36Z
57. Zhao X, Tang Y, You W, et al. Assessment of bone marrow mesenchymal stem cell biological characteristics and support hematopoiesis function in patients with chronic myeloid leukemia Leuk Res. 2006;30:993-1003
58. Jootar S, Pornprasertsud N, Petvises S, et al. Bone marrow derived mesenchymal stem cells from chronic myeloid leukemia t(9;22) patients are devoid of Philadelphia chromosome and support cord blood stem cell expansion. Leuk Res 2006;30:1493-8
59. Krampera M, Glennie S, Dyson J, et al. Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide. Blood 2003;101:3722-9
60. Uccelli A, Moretta L, Pistoia V. Immunoregulatory function of mesenchymal stem cells. Eur J Immunol 2006;36:2566-73
61. Keating A. How do mesenchymal stromal cells suppress T cells? Cell Stem Cell 2008;2:106-8
62. Ryan JM, Barry F, Murphy JM, et al. Interferon-gamma does not break, but promotes the immunosuppressive capacity of adult human mesenchymal stem cells. Clin Exp Immunol 2007;149:353-63
63. Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 2005;105: 1815-22
64. Meisel R, Zibert A, Laryea M, et al. Human bone marrow stromalcells inhibit allogeneic T-cell responses by indoleamine 2, 3-dioxygenase-mediated tryptophan degradation. Blood 2004;103:4619-21
65. Croitoru-Lamoury J, Lamoury FM, Caristo M, et al. Interferon-y regulates the proliferation and differentiation of mesenchymal stem cells via activation of indoleamine 2, 3 dioxygenase (IDO). PLoS One 2011;6(2):e14698
66. Trabanelli S, Ocadlikova D, Ciciarello M, et al. The SOCS3-independent expression of IDO2 supports the homeostatic generation of T regulatory cells by human dendritic cells. J Immunol 2014;192(3): 1231-40
67. Mudry RE, Fortney JE, York T, et al. Stromal cells regulate survival of B-lineage leukemic cells during chemotherapy. Blood 2000;96(5):1926-32
68. Konopleva M, Konoplev S, Hu W, et al. Stromal cells prevent apoptosis of AML cells by up-regulation of anti-apoptotic proteins. Leukemia 2002;16(9):1713-24
69. Nefedova Y, Landowski TH, Dalton WS. Bone marrow stromal-derived soluble factors and direct cell contact contribute to de novo drug resistance of myeloma cells by distinct mechanisms. Leukemia 2003;17(6):1175-82
70. Nwabo Kamdje AH, Mosna F, Bifari F, et al. Notch-3 and Notch-4 signaling rescue from apoptosis human B-ALL cells in contact with human bone marrow-derived mesenchymal stromal cells. Blood 2011; 118(2):380-9
71. Vicente López A, Vázquez Garćia MN, Melen GJ, et al. Mesenchymal stromal cells derived from the bone marrow of acute lymphoblastic leukemia patients show altered BMP4 production: correlations with the course of disease. PLoS ONE 2014;9(1): e84496
72. Yuan Y, Lu X, Tao CL, et al. Forced expression of indoleamine-2, 3-dioxygenase in human umbilical cord-derived mesenchymal stem cells abolishes their anti-apoptotic effect on leukemia cell lines in vitro. In Vitro Cell Dev Biol Anim 2013; 49(10):752-8
73. Valadi H, Ekstrom K, Bossios A, et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 2007;9:654-9
74. Simons M, Raposo G. Exosomes-vesicular carriers for intercellular communication. Curr Opin Cell Biol 2009;21:575-81
75. Lee TH, D'Asti E, Magnus N, et al. Microvesicles as mediators of intercellular communication in cancer-the emerging science of cellular 'debris'. Semin Immunopathol 2011;33:455-67
76. Huan J, Hornick NI, Shurtleff MJ, et al. RNA trafficking by acute myelogenous leukemia exosomes. Cancer Res 2013;73(2): 918-29
77. Di Virgilio F. Purines, Purinergic Receptors, and Cancer. Cancer Res 2012;72(21): 5441-7
78. Ghiringhelli F, Apetoh L, Tesniere A, et al. Activation of the NLRP3 inflammasome in dendritic cells induces IL-1b-dependent adaptive immunity against tumors. Nat Med 2009;15:1170-8
79. Trabanelli S, Ocadĺiková D, Gulinelli S, et al. Extracellular ATP exerts opposite effects on activated and regulatory CD4+ T cells via purinergic P2 receptor activation. J Immunol 2012;189(3):1303-10
80. Di Virgilio F, Ferrari D, Adinolfi E. P2X7: a growth-promoting receptor-implication for cancer. Purinergic Signal 2009;5(2):251-6
81. Chong JH, Zheng GG, Zhu XF, et al. Abnormal expression of P2X family receptors in Chinese pediatric acute leukemias. Biochem Biophys Res Commun 2010;391(1):498-504
82. Salvestrini V, Zini R, Rossi L, et al. Purinergic signaling inhibits human acute myeloblastic leukemia cell proliferation, migration, and engraftment in immunodeficient mice. Blood 2012;119(1): 217-26
83. Alves LA, Bezerra RJ, Faria RX, et al. Physiological roles and potential therapeutic applications of the P2X7 receptor in inflammation and pain. Molecules 2013; 18(9):10953-72
84. Figdor CG, de Vries IJ, Lesterhuis WJ, Melief CJ. Dendritic cell immunotherapy: mapping the way. Nat Med 2004;10(5): 475-80
85. Zitvogel L, Tesniere A, Kroemer G. Cancer despite immunosurveillance: immunoselection and immunosubversion. Nat Rev Immunol 2006;6(10):715-27
86. Dummer W, Niethammer AG, Baccala R, et al. T cell homeostatic proliferation elicits effective antitumor autoimmunity. J Clin Invest 2002;110:185-92
87. Cho BK, Rao VP, Ge Q, et al. Homeostasis-stimulated proliferation drives naive T cells to differentiate directly into memory T cells. J Exp Med 2000;192: 549-56
88. Borrello IM, Levitsky HI, Stock W, et al. Granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting cellular immunotherapy in combination with autologous stem cell transplantation (ASCT) as postremission therapy for acute myeloid leukemia (AML). Blood 2009;114:1736-45
89. Cui Y, Kelleher E, Straley E, et al. Immunotherapy of established tumors using bone marrow transplantation with antigen gene-modified hematopoietic stem cells. Nat Med 2003;9:952-8
90. Vivier E, Raulet DH, Moretta A, et al. Innate or adaptive immunity? The example of natural killer cells. Science 2011; 331(6013):44-9
91. Robertson MJ, Ritz J. Biology and clinical relevance of human natural killer cells. Blood 1990;76:2421-38
92. Lanier LL. NK cell receptors. Annu Rev Immunol 1998;16:359-93
93. Farad SS, Fehniger T, Ruggeri L, et al. Natural killer cell receptors: new biology and insights into graft versus leukemia effect. Blood 2002;100:1935-47
94. Ruggeri L, Capanni M, Urbani E, et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science 2002;295:2097-100
95. Ruggeri L, Capanni M, Casucci M, et al. Role of natural killer cell alloreactivity in HLA-mismatched hematopoietic stem cell transplantation. Blood 1999;94:333-9
96. Miller JS, Soignier Y, Panoskaltsis-Mortari A, et al. Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood 2005;105(8):3051-7
97. Rubnitz JE, Inaba H, Ribeiro RC, et al. NKAML: a pilot study to determine the safety and feasibility of haploidentical natural killer cell transplantation in childhood acute myeloid leukemia. J Clin Oncol 2010;28(6):955-9
98. Curti A, Ruggeri L, D'Addio A, et al. Successful transfer of alloreactive haploidentical KIR ligand-mismatched natural killer cells after infusion in elderly high risk acute myeloid leukemia patients. Blood 2011;118(12):3273-9
99. Kotla V, Goel S, Nischal S, et al. Mechanism of action of lenalidomide in hematological malignancies. J Hematol Oncol 2009;2:36
100. Davies F, Baz R. Lenalidomide mode of action: linking bench and clinical findings. Blood Rev 2010;24(Suppl 1):S13-19
101. Bodera P, Stankiewicz W. Immunomodulatory properties of thalidomide analogs: pomalidomide and lenalidomide, experimental and therapeutic applications. Recent Pat Endocr Metab Immune Drug Discov 2011;5:192-6
102. Ramsay AG, Gribben JG. Immune dysfuction in chronic lymphocytic leukemia T cells and lenalidomide as an immunomodulatory drug. Hematologica 2009;94:1198-202
103. Fehniger TA, Uy GL, Trinkaus K, et al. A phase 2 study of high-dose lenalidomide as initial therapy for older patients with acute myeloid leukemia. Blood 2011;117(6): 1828-33
104. Blum W, Klisovic RB, Becker H, et al. Dose escalation of lenalidomide in relapsed or refractory acute leukemias. J Clin Oncol 2010;28(33):4919-25
105. Pollyea DA, Kohrt HE, Gallegos L, et al. Safety, efficacy and biological predictors of response to sequential azacitidine and lenalidomide for elderly patients with acute myeloid leukemia. Leukemia 2012;26(5): 893-901
106. Ramsingh G, Westervelt P, Cashen AF, et al. A phase 1 study of concomitant high-dose lenalidomide and 5-azacitidine induction in the treatment of AML. Leukemia 2013;27(3):725-8
107. Visani G, Ferrara F, Di Raimondo F, et al. Low-dose lenalidomide plus cytarabine induce complete remission that can be predicted by genetic profiling in elderly acute myeloid leukemia patients. Leukemia 2014;28(4):967-70
108. Fucikova J, Kralikova P, Fialova A, et al. Human tumor cells killed by anthracyclines induce a tumor-specific immune response. Cancer Res 2011;71:4821-33
109. Adinolfi E, Kim M, Young MT, et al. Tyrosine phosphorylation of HSP90 within the P2X7 receptor complex negatively regulates P2X7 receptors. J Biol Chem 2003;278(39):37344-51
110. Wemeau M, Kepp O, Tesnière A, et al. Calreticulin exposure on malignant blasts predicts a cellular anticancer immune response in patients with acute myeloid leukemia. Cell Death Dis 2010;1:e104
111. Zitvogel L, Kepp O, Aymeric L, et al. Integration of host-related signatures with cancer cell-derived predictors for the optimal management of anticancer chemotherapy. Cancer Res 2010;70(23): 9538-43
112. Tesniere A, Schlemmer F, Boige V, et al. Immunogenic death of colon cancer cells treated with oxaliplatin. Oncogene 2010; 29(4):482-91
113. Fredly H, Ersvær E, Gjertsen BT, Bruserud O. Immunogenic apoptosis in human acute myeloid leukemia (AML): primary human AML cells expose calreticulin and release heat shock protein (HSP) 70 and HSP90 during apoptosis. Oncol Rep 2011;25(6):1549-56