Critical role of tumor microenvironment in shaping NK cell functions: Implication of hypoxic stress

Frontiers in Immunology

Volumn 6, Issue SEP, 2015, Pages

  Hasmim, Meriem ^a   Messai, Yosra ^a   Ziani, Linda ^a   Thiery, Jerome ^a   Bouhris, Jean Henri ^a,b   Noman, Muhammad Zaeem ^a   Chouaib, Salem ^a  

^a Faculty of Medicine University of Paris Sud   (France)

^b INSTITUT GUSTAVE ROUSSY   (France)

Author keywords

HIF; Immune suppression; Microenvironment; Natural killer cells; Solid tumors

Indexed keywords

CHEMOKINE RECEPTOR CXCR3; CXCL9 CHEMOKINE; GAMMA INTERFERON INDUCIBLE PROTEIN 10; HYPOXIA INDUCIBLE FACTOR 1ALPHA; HYPOXIA INDUCIBLE FACTOR 2ALPHA; HYPOXIA INDUCIBLE FACTOR 3ALPHA; INTERLEUKIN 10; NATURAL CYTOTOXICITY TRIGGERING RECEPTOR 1; NATURAL CYTOTOXICITY TRIGGERING RECEPTOR 2; NATURAL CYTOTOXICITY TRIGGERING RECEPTOR 3; NATURAL KILLER CELL RECEPTOR NKG2D; TRANSFORMING GROWTH FACTOR BETA;

ADAPTIVE IMMUNITY; CANCER IMMUNOTHERAPY; CANCER RESISTANCE; CD4+ CD25+ T LYMPHOCYTE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL FUNCTION; CELL INFILTRATION; CELLULAR IMMUNITY; DENDRITIC CELL; FIBROBLAST; HUMAN; HYPOXIA; IMMUNE DEFICIENCY; INNATE IMMUNITY; MACROPHAGE; NATURAL KILLER CELL; NATURAL KILLER CELL MEDIATED CYTOTOXICITY; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); POLARIZATION; PROTEIN EXPRESSION; REVIEW; STROMA CELL; SUPPRESSOR CELL; TUMOR CELL DESTRUCTION; TUMOR IMMUNITY; TUMOR MICROENVIRONMENT;

EID: 84946552670     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2015.00482     Document Type: Review

References (107)

1. Moretta L, Montaldo E, Vacca P, Del Zotto G, Moretta F, Merli P, et al. Human natural killer cells: origin, receptors, function, and clinical applications. Int Arch Allergy Immunol (2014) 164:253-64. doi: 10.1159/000365632.
2. Pende D, Marcenaro S, Falco M, Martini S, Bernardo ME, Montagna D, et al. Anti-leukemia activity of alloreactive NK cells in KIR ligand-mismatched haploidentical HSCT for pediatric patients: evaluation of the functional role of activating KIR and redefinition of inhibitory KIR specificity. Blood (2009) 113:3119-29. doi:10.1182/blood-2008-06-164103.
3. Wiltrout RH, Herberman RB, Zhang S, Chirigos MA, Ortaldo JR, Green KM, et al. Role of organ-associated NK cells in decreased formation of experimental metastases in lung and liver. J Immunol (1985) 134:4267-75.
4. Yang Q, Goding SR, Hokland ME, Basse PH. Antitumor activity of NK cells. Immunol Res (2006) 36:13-25. doi:10.1385/IR:36:1:13.
5. Rusakiewicz S, Semeraro M, Sarabi M, Desbois M, Locher C, Mendez R, et al. Immune infiltrates are prognostic factors in localized gastrointestinal stromal tumors. Cancer Res (2013) 73:3499-510. doi:10.1158/0008-5472.CAN-13-0371.
6. Imai K, Matsuyama S, Miyake S, Suga K, Nakachi K. Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population. Lancet (2000) 356:1795-9. doi:10.1016/S0140-6736(00)03231-1.
7. Dithmar SA, Rusciano DA, Armstrong CA, Lynn MJ, Grossniklaus HE. Depletion of NK cell activity results in growth of hepatic micrometastases in a murine ocular melanoma model. Curr Eye Res (1999) 19:426-31. doi:10.1076/ceyr.19.5.426.5294.
8. Kataoka H, Uchino H, Iwamura T, Seiki M, Nabeshima K, Koono M. Enhanced tumor growth and invasiveness in vivo by a carboxyl-terminal fragment of alpha1-proteinase inhibitor generated by matrix metalloproteinases: a possible modulatory role in natural killer cytotoxicity. Am J Pathol (1999) 154:457-68. doi:10.1016/S0002-9440(10)65292-3.
9. Mailloux AW, Clark AM, Young MR. NK depletion results in increased CCL22 secretion and Treg levels in Lewis lung carcinoma via the accumulation of CCL22-secreting CD11b+CD11c+ cells. Int J Cancer (2010) 127:2598-611. doi:10.1002/ijc.25281.
10. Nannmark U, Basse P, Johansson BR, Kuppen P, Kjergaard J, Hokland M. Morphological studies of effector cell-microvessel interactions in adoptive immunotherapy in tumor-bearing animals. Nat Immun (1996) 15:78-86.
11. Wennerberg E, Pfefferle A, Ekblad L, Yoshimoto Y, Kremer V, Kaminskyy VO, et al. Human anaplastic thyroid carcinoma cells are sensitive to NK cell-mediated lysis via ULBP2/5/6 and chemoattract NK cells. Clin Cancer Res (2014) 20:5733-44. doi:10.1158/1078-0432.CCR-14-0291.
12. Wennerberg E, Kremer V, Childs R, Lundqvist A. CXCL10-induced migration of adoptively transferred human natural killer cells toward solid tumors causes regression of tumor growth in vivo. Cancer Immunol Immunother (2015) 64:225-35. doi:10.1007/s00262-014-1629-5.
13. Bingle L, Brown NJ, Lewis CE. The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies. J Pathol (2002) 196:254-65. doi:10.1002/path.1027.
14. Gabrilovich DI, Ostrand-Rosenberg S, Bronte V. Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol (2012) 12:253-68. doi:10.1038/nri3175.
15. Mantovani A, Sozzani S, Locati M, Allavena P, Sica A. Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol (2002) 23:549-55. doi:10.1016/S1471-4906(02)02302-5.
16. Quatromoni JG, Eruslanov E. Tumor-associated macrophages: function, phenotype, and link to prognosis in human lung cancer. Am J Transl Res (2012) 4:376-89.
17. Cekic C, Day YJ, Sag D, Linden J. Myeloid expression of adenosine A2A receptor suppresses T and NK cell responses in the solid tumor microenvironment. Cancer Res (2014) 74:7250-9. doi:10.1158/0008-5472.CAN-13-3583.
18. Mitsuhashi A, Goto H, Kuramoto T, Tabata S, Yukishige S, Abe S, et al. Surfactant protein A suppresses lung cancer progression by regulating the polarization of tumor-associated macrophages. Am J Pathol (2013) 182:1843-53. doi:10.1016/j.ajpath.2013.01.030.
19. Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol (2009) 9:162-74. doi:10.1038/nri2506.
20. Liu C, Yu S, Kappes J, Wang J, Grizzle WE, Zinn KR, et al. Expansion of spleen myeloid suppressor cells represses NK cell cytotoxicity in tumor-bearing host. Blood (2007) 109:4336-42. doi:10.1182/blood-2006-09-046201.
21. Li H, Han Y, Guo Q, Zhang M, Cao X. Cancer-expanded myeloid-derived suppressor cells induce anergy of NK cells through membrane-bound TGF-beta 1. J Immunol (2009) 182:240-9. doi:10.4049/jimmunol.182.1.240.
22. Hoechst B, Voigtlaender T, Ormandy L, Gamrekelashvili J, Zhao F, Wedemeyer H, et al. Myeloid derived suppressor cells inhibit natural killer cells in patients with hepatocellular carcinoma via the NKp30 receptor. Hepatology (2009) 50:799-807. doi:10.1002/hep.23054.
23. Zou W. Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol (2006) 6:295-307. doi:10.1038/nri1806.
24. Trzonkowski P, Szmit E, Mysliwska J, Dobyszuk A, Mysliwski A. CD4+CD25+ T regulatory cells inhibit cytotoxic activity of T CD8+ and NK lymphocytes in the direct cell-to-cell interaction. Clin Immunol (2004) 112:258-67. doi:10.1016/j.clim.2004.04.003.
25. Xu L, Tanaka S, Bonno M, Ido M, Kawai M, Yamamoto H, et al. Cord blood CD4(+)CD25(+) regulatory T cells fail to inhibit cord blood NK cell functions due to insufficient production and expression of TGF-beta1. Cell Immunol (2014) 290:89-95. doi:10.1016/j.cellimm.2014.05.007.
26. Terme M, Chaput N, Combadiere B, Ma A, Ohteki T, Zitvogel L. Regulatory T cells control dendritic cell/NK cell cross-talk in lymph nodes at the steady state by inhibiting CD4+ self-reactive T cells. J Immunol (2008) 180:4679-86. doi:10.4049/jimmunol.180.7.4679.
27. Smyth MJ, Teng MW, Swann J, Kyparissoudis K, Godfrey DI, Hayakawa Y. CD4+CD25+ T regulatory cells suppress NK cell-mediated immunotherapy of cancer. J Immunol (2006) 176:1582-7. doi:10.4049/jimmunol.176.3.1582.
28. Sarhan D, Palma M, Mao Y, Adamson L, Kiessling R, Mellstedt H, et al. Dendritic cell regulation of NK-cell responses involves lymphotoxin-alpha, IL-12 and TGF-beta. Eur J Immunol (2015) 45(6):1783-93. doi:10.1002/eji.201444885.
29. Dumitriu IE, Dunbar DR, Howie SE, Sethi T, Gregory CD. Human dendritic cells produce TGF-beta 1 under the influence of lung carcinoma cells and prime the differentiation of CD4+CD25+Foxp3+ regulatory T cells. J Immunol (2009) 182:2795-807. doi:10.4049/jimmunol.0712671.
30. Zhang X, Huang H, Yuan J, Sun D, Hou WS, Gordon J, et al. CD4-8-dendritic cells prime CD4+ T regulatory 1 cells to suppress antitumor immunity. J Immunol (2005) 175:2931-7. doi:10.4049/jimmunol.175.5.2931.
31. Perez-Martinez A, Iyengar R, Gan K, Chotsampancharoen T, Rooney B, Holladay M, et al. Blood dendritic cells suppress NK cell function and increase the risk of leukemia relapse after hematopoietic cell transplantation. Biol Blood Marrow Transplant (2011) 17:598-607. doi:10.1016/j.bbmt.2010.10.019.
32. Anguille S, Van Acker HH, Van Den Bergh J, Willemen Y, Goossens H, Van Tendeloo VF, et al. Interleukin-15 dendritic cells harness NK cell cytotoxic effector function in a contact-and IL-15-dependent manner. PLoS One (2015) 10:e0123340. doi:10.1371/journal.pone.0123340.
33. Ferlazzo G, Tsang ML, Moretta L, Melioli G, Steinman RM, Munz C. Human dendritic cells activate resting natural killer (NK) cells and are recognized via the NKp30 receptor by activated NK cells. J Exp Med (2002) 195:343-51. doi:10.1084/jem.20011149.
34. Franco OE, Shaw AK, Strand DW, Hayward SW. Cancer associated fibroblasts in cancer pathogenesis. Semin Cell Dev Biol (2010) 21:33-9. doi:10.1016/j.semcdb.2009.10.010.
35. Rasanen K, Vaheri A. Activation of fibroblasts in cancer stroma. Exp Cell Res (2010) 316:2713-22. doi:10.1016/j.yexcr.2010.04.032.
36. Polanska UM, Orimo A. Carcinoma-associated fibroblasts: non-neoplastic tumour-promoting mesenchymal cells. J Cell Physiol (2013) 228:1651-7. doi:10.1002/jcp.24347.
37. Madar S, Goldstein I, Rotter V. 'Cancer associated fibroblasts'-more than meets the eye. Trends Mol Med (2013) 19:447-53. doi:10.1016/j.molmed.2013.05.004.
38. Augsten M. Cancer-associated fibroblasts as another polarized cell type of the tumor microenvironment. Front Oncol (2014) 4:62. doi:10.3389/fonc.2014.00062.
39. Shimoda M, Mellody KT, Orimo A. Carcinoma-associated fibroblasts are a rate-limiting determinant for tumour progression. Semin Cell Dev Biol (2010) 21:19-25. doi:10.1016/j.semcdb.2009.10.002.
40. Valcz G, Sipos F, Tulassay Z, Molnar B, Yagi Y. Importance of carcinoma-associated fibroblast-derived proteins in clinical oncology. J Clin Pathol (2014) 67:1026-31. doi:10.1136/jclinpath-2014-202561.
41. Harper J, Sainson RC. Regulation of the anti-tumour immune response by cancer-associated fibroblasts. Semin Cancer Biol (2014) 25:69-77. doi:10.1016/j.semcancer.2013.12.005.
42. Kraman M, Bambrough PJ, Arnold JN, Roberts EW, Magiera L, Jones JO, et al. Suppression of antitumor immunity by stromal cells expressing fibroblast activation protein-alpha. Science (2010) 330:827-30. doi:10.1126/science.1195300.
43. Flavell RA, Sanjabi S, Wrzesinski SH, Licona-Limon P. The polarization of immune cells in the tumour environment by TGFbeta. Nat Rev Immunol (2010) 10:554-67. doi:10.1038/nri2808.
44. Park YP, Choi SC, Kiesler P, Gil-Krzewska A, Borrego F, Weck J, et al. Complex regulation of human NKG2D-DAP10 cell surface expression: opposing roles of the gammac cytokines and TGF-beta1. Blood (2011) 118:3019-27. doi:10.1182/blood-2011-04-346825.
45. Balsamo M, Scordamaglia F, Pietra G, Manzini C, Cantoni C, Boitano M, et al. Melanoma-associated fibroblasts modulate NK cell phenotype and antitumor cytotoxicity. Proc Natl Acad Sci U S A (2009) 106:20847-52. doi:10.1073/pnas.0906481106.
46. Li T, Yang Y, Hua X, Wang G, Liu W, Jia C, et al. Hepatocellular carcinoma-associated fibroblasts trigger NK cell dysfunction via PGE2 and IDO. Cancer Lett (2012) 318:154-61. doi:10.1016/j.canlet.2011.12.020.
47. Li T, Yi S, Liu W, Jia C, Wang G, Hua X, et al. Colorectal carcinoma-derived fibroblasts modulate natural killer cell phenotype and antitumor cytotoxicity. Med Oncol (2013) 30:663. doi:10.1007/s12032-013-0663-z.
48. Raulet DH, Gasser S, Gowen BG, Deng W, Jung H. Regulation of ligands for the NKG2D activating receptor. Annu Rev Immunol (2013) 31:413-41. doi:10.1146/annurev-immunol-032712-095951.
49. Benson DM Jr, Bakan CE, Mishra A, Hofmeister CC, Efebera Y, Becknell B, et al. The PD-1/PD-L1 axis modulates the natural killer cell versus multiple myeloma effect: a therapeutic target for CT-011, a novel monoclonal anti-PD-1 antibody. Blood (2010) 116:2286-94. doi:10.1182/blood-2010-02-271874.
50. Castriconi R, Dondero A, Bellora F, Moretta L, Castellano A, Locatelli F, et al. Neuroblastoma-derived TGF-beta1 modulates the chemokine receptor repertoire of human resting NK cells. J Immunol (2013) 190:5321-8. doi:10.4049/jimmunol.1202693.
51. Pietra G, Manzini C, Rivara S, Vitale M, Cantoni C, Petretto A, et al. Melanoma cells inhibit natural killer cell function by modulating the expression of activating receptors and cytolytic activity. Cancer Res (2012) 72:1407-15. doi:10.1158/0008-5472.CAN-11-2544.
52. Groh V, Wu J, Yee C, Spies T. Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation. Nature (2002) 419:734-8. doi:10.1038/nature01112.
53. Song H, Kim J, Cosman D, Choi I. Soluble ULBP suppresses natural killer cell activity via down-regulating NKG2D expression. Cell Immunol (2006) 239:22-30. doi:10.1016/j.cellimm.2006.03.002.
54. Pogge Von Strandmann E, Simhadri VR, Von Tresckow B, Sasse S, Reiners KS, Hansen HP, et al. Human leukocyte antigen-B-associated transcript 3 is released from tumor cells and engages the NKp30 receptor on natural killer cells. Immunity (2007) 27:965-74. doi:10.1016/j.immuni.2007.10.010.
55. Deng W, Gowen BG, Zhang L, Wang L, Lau S, Iannello A, et al. Antitumor immunity. A shed NKG2D ligand that promotes natural killer cell activation and tumor rejection. Science (2015) 348:136-9. doi:10.1126/science.1258867.
56. Nanbakhsh A, Pochon C, Mallavialle A, Amsellem S, Bourhis JH, Chouaib S. c-Myc regulates expression of NKG2D ligands ULBP1/2/3 in AML and modulates their susceptibility to NK-mediated lysis. Blood (2014) 123:3585-95. doi:10.1182/blood-2013-11-536219.
57. Noman MZ, Messai Y, Carre T, Akalay I, Meron M, Janji B, et al. Microenvironmental hypoxia orchestrating the cell stroma cross talk, tumor progression and antitumor response. Crit Rev Immunol (2011) 31:357-77. doi:10.1615/CritRevImmunol.v31.i5.10.
58. Laconi E. The evolving concept of tumor microenvironments. Bioessays (2007) 29:738-44. doi:10.1002/bies.20606.
59. Graeber TG, Osmanian C, Jacks T, Housman DE, Koch CJ, Lowe SW, et al. Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours. Nature (1996) 379:88-91. doi:10.1038/379088a0.
60. Erler JT, Cawthorne CJ, Williams KJ, Koritzinsky M, Wouters BG, Wilson C, et al. Hypoxia-mediated down-regulation of Bid and Bax in tumors occurs via hypoxia-inducible factor 1-dependent and-independent mechanisms and contributes to drug resistance. Mol Cell Biol (2004) 24:2875-89. doi:10.1128/MCB.24.7.2875-2889.2004.
61. Semenza GL. Hypoxia, clonal selection, and the role of HIF-1 in tumor progression. Crit Rev Biochem Mol Biol (2000) 35:71-103. doi:10.1080/10409230091169186.
62. Pennacchietti S, Michieli P, Galluzzo M, Mazzone M, Giordano S, Comoglio PM. Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene. Cancer Cell (2003) 3:347-61. doi:10.1016/S1535-6108(03)00085-0.
63. Hill RP, Marie-Egyptienne DT, Hedley DW. Cancer stem cells, hypoxia and metastasis. Semin Radiat Oncol (2009) 19:106-11. doi:10.1016/j.semradonc.2008.12.002.
64. Bristow RG, Hill RP. Hypoxia and metabolism. Hypoxia, DNA repair and genetic instability. Nat Rev Cancer (2008) 8:180-92. doi:10.1038/nrc2344.
65. Wenger RH, Gassmann M. Oxygen(es) and the hypoxia-inducible factor-1. Biol Chem (1997) 378:609-16.
66. Mahon PC, Hirota K, Semenza GL. FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity. Genes Dev (2001) 15:2675-86. doi:10.1101/gad.924501.
67. Lando D, Peet DJ, Gorman JJ, Whelan DA, Whitelaw ML, Bruick RK. FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor. Genes Dev (2002) 16:1466-71. doi:10.1101/gad.991402.
68. Lando D, Peet DJ, Whelan DA, Gorman JJ, Whitelaw ML. Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch. Science (2002) 295:858-61. doi:10.1126/science.1068592.
69. Keith B, Johnson RS, Simon MC. HIF1a and HIF2a: sibling rivalry in hypoxic tumour growth and progression. Nat Rev Cancer (2011) 12:9-22. doi:10.1038/nrc3183.
70. Maynard MA, Evans AJ, Shi W, Kim WY, Liu FF, Ohh M. Dominant-negative HIF-3 alpha 4 suppresses VHL-null renal cell carcinoma progression. Cell Cycle (2007) 6:2810-6. doi:10.4161/cc.6.22.4947.
71. Fink T, Ebbesen P, Koppelhus U, Zachar V. Natural killer cell-mediated basal and interferon-enhanced cytotoxicity against liver cancer cells is significantly impaired under in vivo oxygen conditions. Scand J Immunol (2003) 58:607-12. doi:10.1111/j.1365-3083.2003.01347.x.
72. Yamada N, Yamanegi K, Ohyama H, Hata M, Nakasho K, Futani H, et al. Hypoxia downregulates the expression of cell surface MICA without increasing soluble MICA in osteosarcoma cells in a HIF-1alpha-dependent manner. Int J Oncol (2012) 41:2005-12. doi:10.3892/ijo.2012.1630.
73. Noman MZ, Janji B, Kaminska B, Van Moer K, Pierson S, Przanowski P, et al. Blocking hypoxia-induced autophagy in tumors restores cytotoxic T-cell activity and promotes regression. Cancer Res (2011) 71:5976-86. doi:10.1158/0008-5472.CAN-11-1094.
74. Baginska J, Viry E, Berchem G, Poli A, Noman MZ, Van Moer K, et al. Granzyme B degradation by autophagy decreases tumor cell susceptibility to natural killer-mediated lysis under hypoxia. Proc Natl Acad Sci U S A (2013) 110:17450-5. doi:10.1073/pnas.1304790110.
75. Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, et al. Cancer statistics, 2006. CA Cancer J Clin (2006) 56:106-30. doi:10.3322/canjclin.56.2.106.
76. Kaelin WG Jr. The von Hippel-Lindau tumor suppressor protein and clear cell renal carcinoma. Clin Cancer Res (2007) 13:680s-4s. doi:10.1158/1078-0432.CCR-06-1865.
77. Tanimoto K, Makino Y, Pereira T, Poellinger L. Mechanism of regulation of the hypoxia-inducible factor-1 alpha by the von Hippel-Lindau tumor suppressor protein. EMBO J (2000) 19:4298-309. doi:10.1093/emboj/19.16.4298.
78. Messai Y, Noman MZ, Hasmim M, Janji B, Tittarelli A, Boutet M, et al. ITPR1 protects renal cancer cells against natural killer cells by inducing autophagy. Cancer Res (2014) 74:6820-32. doi:10.1158/0008-5472.CAN-14-0303.
79. Luo L, Lu J, Wei L, Long D, Guo JY, Shan J, et al. The role of HIF-1 in up-regulating MICA expression on human renal proximal tubular epithelial cells during hypoxia/reoxygenation. BMC Cell Biol (2010) 11:91. doi:10.1186/1471-2121-11-91.
80. Balsamo M, Manzini C, Pietra G, Raggi F, Blengio F, Mingari MC, et al. Hypoxia downregulates the expression of activating receptors involved in NK-cell-mediated target cell killing without affecting ADCC. Eur J Immunol (2013) 43:2756-64. doi:10.1002/eji.201343448.
81. Sceneay J, Chow MT, Chen A, Halse HM, Wong CS, Andrews DM, et al. Primary tumor hypoxia recruits CD11b+/Ly6Cmed/Ly6G+ immune suppressor cells and compromises NK cell cytotoxicity in the premetastatic niche. Cancer Res (2012) 72:3906-11. doi:10.1158/0008-5472.CAN-11-3873.
82. Sarkar S, Germeraad WT, Rouschop KM, Steeghs EM, Van Gelder M, Bos GM, et al. Hypoxia induced impairment of NK cell cytotoxicity against multiple myeloma can be overcome by IL-2 activation of the NK cells. PLoS One (2013) 8:e64835. doi:10.1371/journal.pone.0064835.
83. Finlay DK, Rosenzweig E, Sinclair LV, Feijoo-Carnero C, Hukelmann JL, Rolf J, et al. PDK1 regulation of mTOR and hypoxia-inducible factor 1 integrate metabolism and migration of CD8+ T cells. J Exp Med (2012) 209:2441-53. doi:10.1084/jem.20112607.
84. Hasmim M, Noman MZ, Messai Y, Bordereaux D, Gros G, Baud V, et al. Cutting edge: hypoxia-induced Nanog favors the intratumoral infiltration of regulatory T cells and macrophages via direct regulation of TGF-beta1. J Immunol (2013) 191:5802-6. doi:10.4049/jimmunol.1302140.
85. Matsuoka J, Yashiro M, Doi Y, Fuyuhiro Y, Kato Y, Shinto O, et al. Hypoxia stimulates the EMT of gastric cancer cells through autocrine TGFbeta signaling. PLoS One (2013) 8:e62310. doi:10.1371/journal.pone.0062310.
86. Maurus CF, Schmidt D, Schneider MK, Turina MI, Seebach JD, Zund G. Hypoxia and reoxygenation do not upregulate adhesion molecules and natural killer cell adhesion on human endothelial cells in vitro. Eur J Cardiothorac Surg (2003) 23:976-83. doi:10.1016/S1010-7940(03)00146-5.
87. Gajewski TF, Schreiber H, Fu YX. Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol (2013) 14:1014-22. doi:10.1038/ni.2703.
88. Vitale M, Cantoni C, Pietra G, Mingari MC, Moretta L. Effect of tumor cells and tumor microenvironment on NK-cell function. Eur J Immunol (2014) 44:1582-92. doi:10.1002/eji.201344272.
89. Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science (2011) 331:1565-70. doi:10.1126/science.1203486.
90. Smyth MJ, Wallace ME, Nutt SL, Yagita H, Godfrey DI, Hayakawa Y. Sequential activation of NKT cells and NK cells provides effective innate immunotherapy of cancer. J Exp Med (2005) 201:1973-85. doi:10.1084/jem.20042280.
91. Iguchi-Manaka A, Kai H, Yamashita Y, Shibata K, Tahara-Hanaoka S, Honda S, et al. Accelerated tumor growth in mice deficient in DNAM-1 receptor. J Exp Med (2008) 205:2959-64. doi:10.1084/jem.20081611.
92. Guillerey C, Smyth MJ. NK cells and cancer immunoediting. Curr Top Microbiol Immunol (2015). doi:10.1007/82_2015_446.
93. Ghadially H, Ohana M, Elboim M, Gazit R, Gur C, Nagler A, et al. NK cell receptor NKp46 regulates graft-versus-host disease. Cell Rep (2014) 7:1809-14. doi:10.1016/j.celrep.2014.05.011.
94. Elboim M, Gazit R, Gur C, Ghadially H, Betser-Cohen G, Mandelboim O. Tumor immunoediting by NKp46. J Immunol (2010) 184:5637-44. doi:10.4049/jimmunol.0901644.
95. Buchser WJ, Laskow TC, Pavlik PJ, Lin HM, Lotze MT. Cell-mediated autophagy promotes cancer cell survival. Cancer Res (2012) 72:2970-9. doi:10.1158/0008-5472.CAN-11-3396.
96. Khaznadar Z, Henry G, Setterblad N, Agaugue S, Raffoux E, Boissel N, et al. Acute myeloid leukemia impairs natural killer cells through the formation of a deficient cytotoxic immunological synapse. Eur J Immunol (2014) 44:3068-80. doi:10.1002/eji.201444500.
97. Ruggeri L, Mancusi A, Capanni M, Martelli MF, Velardi A. Exploitation of alloreactive NK cells in adoptive immunotherapy of cancer. Curr Opin Immunol (2005) 17:211-7. doi:10.1016/j.coi.2005.01.007.
98. Aversa F, Terenzi A, Tabilio A, Falzetti F, Carotti A, Ballanti S, et al. Full haplotype-mismatched hematopoietic stem-cell transplantation: a phase II study in patients with acute leukemia at high risk of relapse. J Clin Oncol (2005) 23:3447-54. doi:10.1200/JCO.2005.09.117.
99. Curti A, Ruggeri L, D'addio A, Bontadini A, Dan E, Motta MR, 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) 118:3273-9. doi:10.1182/blood-2011-01-329508.
100. Laport GG, Sheehan K, Baker J, Armstrong R, Wong RM, Lowsky R, et al. Adoptive immunotherapy with cytokine-induced killer cells for patients with relapsed hematologic malignancies after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant (2011) 17:1679-87. doi:10.1016/j.bbmt.2011.05.012.
101. Geller MA, Miller JS. Use of allogeneic NK cells for cancer immunotherapy. Immunotherapy (2011) 3:1445-59. doi:10.2217/imt.11.131.
102. Cho D, Shook DR, Shimasaki N, Chang YH, Fujisaki H, Campana D. Cytotoxicity of activated natural killer cells against pediatric solid tumors. Clin Cancer Res (2010) 16:3901-9. doi:10.1158/1078-0432.CCR-10-0735.
103. Geller MA, Cooley S, Judson PL, Ghebre R, Carson LF, Argenta PA, et al. A phase II study of allogeneic natural killer cell therapy to treat patients with recurrent ovarian and breast cancer. Cytotherapy (2011) 13:98-107. doi:10.3109/14653249.2010.515582.
104. Terme M, Ullrich E, Delahaye NF, Chaput N, Zitvogel L. Natural killer cell-directed therapies: moving from unexpected results to successful strategies. Nat Immunol (2008) 9:486-94. doi:10.1038/ni1580.
105. Sun X, Kanwar JR, Leung E, Lehnert K, Wang D, Krissansen GW. Gene transfer of antisense hypoxia inducible factor-1 alpha enhances the therapeutic efficacy of cancer immunotherapy. Gene Ther (2001) 8:638-45. doi:10.1038/sj.gt.3301388.
106. Patiar S, Harris AL. Role of hypoxia-inducible factor-1alpha as a cancer therapy target. Endocr Relat Cancer (2006) 13(Suppl 1):S61-75. doi:10.1677/erc.1.01290.
107. Scholz CC, Taylor CT. Targeting the HIF pathway in inflammation and immunity. Curr Opin Pharmacol (2013) 13:646-53. doi:10.1016/j.coph.2013.04.009.