Ionizing radiation sensitizes tumors to PD-L1 immune checkpoint blockade in orthotopic murine head and neck squamous cell carcinoma

OncoImmunology

Volumn 6, Issue 10, 2017, Pages

  Oweida, Ayman ^a   Lennon, Shelby ^a   Calame, Dylan ^a   Korpela, Sean ^a   Bhatia, Shilpa ^a   Sharma, Jaspreet ^a   Graham, Caleb ^b   Binder, David ^a   Serkova, Natalie ^a,b   Raben, David ^a   Heasley, Lynn ^a   Clambey, Eric ^b   Nemenoff, Raphael ^b   Karam, Sana D ^a  

^a UNIVERSITY OF COLORADO   (United States)

^b UNIVERSITY OF COLORADO SCHOOL OF MEDICINE   (United States)

Author keywords

head and neck cancer; immune checkpoint inhibitors; PD L1; Radiotherapy

Indexed keywords

PROGRAMMED DEATH 1 LIGAND 1;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CONTROLLED STUDY; DOWN REGULATION; ENZYME LINKED IMMUNOSORBENT ASSAY; FEMALE; FLOW CYTOMETRY; HEAD AND NECK CANCER; HISTOPATHOLOGY; IMMUNOHISTOCHEMISTRY; IONIZING RADIATION; IRRADIATION; LYMPHOCYTIC INFILTRATION; MOUSE; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; REAL TIME POLYMERASE CHAIN REACTION; UPREGULATION;

EID: 85028530585     PISSN: 21624011     EISSN: 2162402X     Source Type: Journal    
DOI: 10.1080/2162402X.2017.1356153     Document Type: Article

References (59)

1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74-108. doi:10.3322/canjclin.55.2.74. PMID:15761078
2. Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents: Defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol. 2006;24(14):2137-50. doi:10.1200/JCO.2005.05.2308. PMID:16682732
3. Taube JM, Klein A, Brahmer JR, Xu H, Pan X, Kim JH, Chen L, Pardoll DM, Topalian SL, Anders RA. Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy. Clin Cancer Res. 2014;20(19):5064-74. doi:10.1158/1078-0432.CCR-13-3271. PMID:24714771
4. Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, Sharfman WH, Brahmer JR, Lawrence DP, Atkins MB, Powderly JD, et al. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol. 2014;32(10):1020-30. doi:10.1200/JCO.2013.53.0105. PMID:24590637
5. Li H, Chiappinelli KB, Guzzetta AA, Easwaran H, Yen RW, Vatapalli R, Topper MJ, Luo J, Connolly RM, Azad NS, et al. Immune regulation by low doses of the DNA methyltransferase inhibitor 5-azacitidine in common human epithelial cancers. Oncotarget. 2014;5(3):587-98. doi:10.18632/oncotarget.1782. PMID:24583822
6. Swanson MS, Sinha UK. Rationale for combined blockade of PD-1 and CTLA-4 in advanced head and neck squamous cell cancer-review of current data. Oral Oncol. 2015;51(1):12-15. doi:10.1016/j.oraloncology.2014.10.010. PMID:25459157
7. Concha-Benavente F, Srivastava RM, Trivedi S, Lei Y, Chandran U, Seethala RR, Freeman GJ, Ferris RL. Identification of the cell-intrinsic and -extrinsic pathways downstream of EGFR and IFNgamma that induce PD-L1 expression in head and neck cancer. Cancer Res. 2016;76(5):1031-43. doi:10.1158/0008-5472.CAN-15-2001
8. Oguejiofor K, Hall J, Slater C, Betts G, Hall G, Slevin N, Dovedi S, Stern PL, West CM. Stromal infiltration of CD8 T cells is associated with improved clinical outcome in HPV-positive oropharyngeal squamous carcinoma. Br J Cancer. 2015;113(6):886-93. doi:10.1038/bjc.2015.277. PMID:26313665
9. Ferris R, Blumenschein G, Fayette J, Guigay J, Colevas A, Licitra L, Harrington K, Kasper S, Vokes E, Even C. Further evaluations of nivolumab (nivo) versus investigator's choice (IC) chemotherapy for recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN): CheckMate 141. J Clin Oncol. 2016;34(suppl; abstr 6009).
10. Gajewski TF, Schreiber H, Fu YX. Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol. 2013;14(10):1014-22. doi:10.1038/ni.2703. PMID:24048123
11. Weichselbaum RR, Liang H, Deng L, Fu YX. Radiotherapy and immunotherapy: A beneficial liaison? Nat Rev Clin Oncol. 2017;14(6):365-79. doi:10.1038/nrclinonc.2016.211. PMID:28094262.
12. Twyman-Saint Victor C, Rech AJ, Maity A, Rengan R, Pauken KE, Stelekati E, Benci JL, Xu B, Dada H, Odorizzi PM, et al. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature. 2015;520(7547):373-7. doi:10.1038/nature14292. PMID:25754329
13. Deng L, Liang H, Burnette B, Beckett M, Darga T, Weichselbaum RR, Fu YX. Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice. J Clin Invest. 2014;124(2):687-95. doi:10.1172/JCI67313. PMID:24382348
14. Lee Y, Auh SL, Wang Y, Burnette B, Wang Y, Meng Y, Beckett M, Sharma R, Chin R, Tu T, et al. Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: Changing strategies for cancer treatment. Blood. 2009;114(3):589-95. doi:10.1182/blood-2009-02-206870. PMID:19349616
15. Golden EB, Frances D, Pellicciotta I, Demaria S, Helen Barcellos-Hoff M, Formenti SC. Radiation fosters dose-dependent and chemotherapy-induced immunogenic cell death. Oncoimmunology. 2014;3:e28518. doi:10.4161/onci.28518. PMID:25071979
16. Wang X, Schoenhals JE, Li A, Valdecanas DR, Ye H, Zang F, Tang C, Tang M, Liu CG, Liu X, et al. Suppression of type I IFN signaling in tumors mediates resistance to anti-PD-1 treatment that can be overcome by radiotherapy. Cancer Res. 2017;77(4):839-50. doi:10.1158/0008-5472.CAN-15-3142. PMID:27821490
17. Dovedi SJ, Adlard AL, Lipowska-Bhalla G, McKenna C, Jones S, Cheadle EJ, Stratford IJ, Poon E, Morrow M, Stewart R, et al. Acquired resistance to fractionated radiotherapy can be overcome by concurrent PD-L1 blockade. Cancer Res. 2014;74(19):5458-68. doi:10.1158/0008-5472.CAN-14-1258. PMID:25274032
18. Curry JM, Sprandio J, Cognetti D, Luginbuhl A, Bar-ad V, Pribitkin E, Tuluc M. Tumor microenvironment in head and neck squamous cell carcinoma. Semin Oncol. 2014;41(2):217-34. doi:10.1053/j.seminoncol.2014.03.003. PMID:24787294
19. Newman AM, Liu CL, Green MR, Gentles AJ, Feng W, Xu Y, Hoang CD, Diehn M, Alizadeh AA. Robust enumeration of cell subsets from tissue expression profiles. Nat Methods. 2015;12(5):453-7. doi:10.1038/nmeth.3337. PMID:25822800
20. Chen Z, Smith CW, Kiel D, Van Waes C. Metastatic variants derived following in vivo tumor progression of an in vitro transformed squamous cell carcinoma line acquire a differential growth advantage requiring tumor-host interaction. Clin Exp Metastasis. 1997;15(5):527-37. doi:10.1023/A:1018474910432. PMID:9247255
21. Thomas GR, Chen Z, Oechsli MN, Hendler FJ, Van Waes C. Decreased expression of CD80 is a marker for increased tumorigenicity in a new murine model of oral squamous-cell carcinoma. Int J Cancer. 1999;82(3):377-84. doi:10.1002/(SICI)1097-0215(19990730)82:3%3c377::AID-IJC11%3e3.0.CO;2-9. PMID:10399955
22. Petit V, Massonnet G, Maciorowski Z, Touhami J, Thuleau A, Nemati F, Laval J, Chateau-Joubert S, Servely JL, Vallerand D, et al. Optimization of tumor xenograft dissociation for the profiling of cell surface markers and nutrient transporters. Lab Invest. 2013;93(5):611-21. doi:10.1038/labinvest.2013.44. PMID:23459372
23. Clark WR, Walsh CM, Glass AA, Huang MT, Ahmed R, Matloubian M. Cell-mediated cytotoxicity in perforin-less mice. Int Rev Immunol. 1995;13(1):1-14. doi:10.3109/08830189509061734. PMID:7494105
24. Tishon A, Lewicki H, Rall G, Von Herrath M, Oldstone MB. An essential role for type 1 interferon-gamma in terminating persistent viral infection. Virology. 1995;212(1):244-50. doi:10.1006/viro.1995.1477. PMID:7676639
25. Dong G, Loukinova E, Chen Z, Gangi L, Chanturita TI, Liu ET, Van Waes C. Molecular profiling of transformed and metastatic murine squamous carcinoma cells by differential display and cDNA microarray reveals altered expression of multiple genes related to growth, apoptosis, angiogenesis, and the NF-kappaB signal pathway. Cancer Res. 2001;61(12):4797-808. doi:10.1158/0008-5472.CAN-04-4621. PMID:11406555
26. Al-Batran SE, Rafiyan MR, Atmaca A, Neumann A, Karbach J, Bender A, Weidmann E, Altmannsberger HM, Knuth A, Jager E. Intratumoral T-cell infiltrates and MHC class I expression in patients with stage IV melanoma. Cancer Res. 2005;65(9):3937-41. doi:10.1158/0008-5472.CAN-04-4621. PMID:15867394.
27. Lee SJ, Jang BC, Lee SW, Yang YI, Suh SI, Park YM, Oh S, Shin JG, Yao S, Chen L, et al. Interferon regulatory factor-1 is prerequisite to the constitutive expression and IFN-gamma-induced upregulation of B7-H1 (CD274). FEBS Lett. 2006;580(3):755-62. doi:10.1016/j.febslet.2005.12.093. PMID:16413538
28. Postow MA, Callahan MK, Wolchok JD. Immune checkpoint blockade in cancer therapy. J Clin Oncol. 2015;33(17):1974-82. doi:10.1200/JCO.2014.59.4358. PMID:25605845
29. Snyder A, Makarov V, Merghoub T, Yuan J, Zaretsky JM, Desrichard A, Walsh LA, Postow MA, Wong P, Ho TS, et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med. 2014;371(23):2189-99. doi:10.1056/NEJMoa1406498. PMID:25409260
30. Ribas A, Hu-Lieskovan S. What does PD-L1 positive or negative mean? J Exp Med. 2016;213(13):2835-40. doi:10.1084/jem.20161462. PMID:27903604
31. Gajewski TF. The next hurdle in cancer immunotherapy: Overcoming the non-T-cell-inflamed tumor microenvironment. Semin Oncol. 2015;42(4):663-71. doi:10.1053/j.seminoncol.2015.05.011. PMID:26320069
32. Herbst RS, Soria JC, Kowanetz M, Fine GD, Hamid O, Gordon MS, Sosman JA, McDermott DF, Powderly JD, Gettinger SN, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014;515(7528):563-7. doi:10.1038/nature14011. PMID:25428504
33. Oguejiofor K, Galletta-Williams H, Dovedi SJ, Roberts DL, Stern PL, West CM. Distinct patterns of infiltrating CD8+ T cells in HPV+ and CD68 macrophages in HPV- oropharyngeal squamous cell carcinomas are associated with better clinical outcome but PD-L1 expression is not prognostic. Oncotarget. 2017;8(9):14416-27. doi:10.18632/oncotarget.14796. PMID:28122336.
34. Balermpas P, Rodel F, Rodel C, Krause M, Linge A, Lohaus F, Baumann M, Tinhofer I, Budach V, Gkika E, et al. CD8+ tumour-infiltrating lymphocytes in relation to HPV status and clinical outcome in patients with head and neck cancer after postoperative chemoradiotherapy: A multicentre study of the German cancer consortium radiation oncology group (DKTK-ROG). Int J Cancer. 2016;138(1):171-81. doi:10.1002/ijc.29683. PMID:26178914
35. Lyford-Pike S, Peng S, Young GD, Taube JM, Westra WH, Akpeng B, Bruno TC, Richmon JD, Wang H, Bishop JA, et al. Evidence for a role of the PD-1:PD-L1 pathway in immune resistance of HPV-associated head and neck squamous cell carcinoma. Cancer Res. 2013;73(6):1733-41. doi:10.1158/0008-5472.CAN-12-2384
36. Mandal R, Senbabaoglu Y, Desrichard A, Havel JJ, Dalin MG, Riaz N, Lee KW, Ganly I, Hakimi AA, Chan TA, et al. The head and neck cancer immune landscape and its immunotherapeutic implications. JCI Insight. 2016;1(17):e89829. doi:10.1172/jci.insight.89829. PMID:27777979
37. Hodge JW, Ardiani A, Farsaci B, Kwilas AR, Gameiro SR. The tipping point for combination therapy: Cancer vaccines with radiation, chemotherapy, or targeted small molecule inhibitors. Semin Oncol. 2012;39(3):323-39. doi:10.1053/j.seminoncol.2012.02.006. PMID:22595055
38. Derer A, Frey B, Fietkau R, Gaipl US. Immune-modulating properties of ionizing radiation: Rationale for the treatment of cancer by combination radiotherapy and immune checkpoint inhibitors. Cancer Immunol Immunother. 2016;65:779-86. doi:10.1007/s00262-015-1771-8. PMID:26590829.
39. Pfister DG, Spencer S, Brizel DM, Burtness B, Busse PM, Caudell JJ, Cmelak AJ, Colevas AD, Dunphy F, Eisele DW, et al. Head and neck cancers, version 2. 2014. Clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2014;12(10):1454-87. doi:10.6004/jnccn.2014.0142. PMID:25313184
40. Crocenzi T, Cottam B, Newell P, Wolf RF, Hansen PD, Hammill C, Solhjem MC, To YY, Greathouse A, Tormoen G, et al. A hypofractionated radiation regimen avoids the lymphopenia associated with neoadjuvant chemoradiation therapy of borderline resectable and locally advanced pancreatic adenocarcinoma. J Immunother Cancer. 2016;4:45. doi:10.1186/s40425-016-0149-6. PMID:27532020
41. Wild AT, Ye X, Ellsworth SG, Smith JA, Narang AK, Garg T, Campian J, Laheru DA, Zheng L, Wolfgang CL, et al. The association between chemoradiation-related lymphopenia and clinical outcomes in patients with locally advanced pancreatic adenocarcinoma. Am J Clin Oncol. 2015;38(3):259-65. doi:10.1097/COC.0b013e3182940ff9. PMID:23648440
42. Stewart CC, Perez CA. Effect of irradiation on immune responses. Radiology. 1976;118(1):201-10. doi:10.1148/118.1.201. PMID:1105662
43. Savage AM, Pritchard JA, Deeley TJ, Davies BH. Immunological state of patients with carcinoma of the bronchus before and after radiotherapy. Thorax. 1980;35(7):500-5. doi:10.1136/thx.35.7.500. PMID:7434311
44. Hoppe RT, Fuks ZY, Strober S, Kaplan HS. The long term effects of radiation of T and B lymphocytes in the peripheral blood after regional irradiation. Cancer. 1977;40(5):2071-8. doi:10.1002/1097-0142(197711)40:5%3c2071::AID-CNCR2820400513%3e3.0.CO;2-V. PMID:144554
45. Grossman SA, Ellsworth S, Campian J, Wild AT, Herman JM, Laheru D, Brock M, Balmanoukian A, Ye X. Survival in patients with severe lymphopenia following treatment with radiation and chemotherapy for newly diagnosed solid tumors. J Natl Compr Canc Netw. 2015;13(10):1225-31. doi:10.3109/07357907.2012.762780. PMID:26483062
46. Yovino S, Kleinberg L, Grossman SA, Narayanan M, Ford E. The etiology of treatment-related lymphopenia in patients with malignant gliomas: Modeling radiation dose to circulating lymphocytes explains clinical observations and suggests methods of modifying the impact of radiation on immune cells. Cancer Invest. 2013;31(2):140-4. doi:10.3109/07357907.2012.762780. PMID:23362951
47. Lugade AA, Moran JP, Gerber SA, Rose RC, Frelinger JG, Lord EM. Local radiation therapy of B16 melanoma tumors increases the generation of tumor antigen-specific effector cells that traffic to the tumor. J Immunol. 2005;174(12):7516-23. doi:10.4049/jimmunol.174.12.7516. PMID:15944250
48. Machtay M, Moughan J, Trotti A, Garden AS, Weber RS, Cooper JS, Forastiere A, Ang KK. Factors associated with severe late toxicity after concurrent chemoradiation for locally advanced head and neck cancer: An RTOG analysis. J Clin Oncol. 2008;26(21):3582-9. doi:10.1200/JCO.2007.14.8841. PMID:18559875
49. Lechner MG, Karimi SS, Barry-Holson K, Angell TE, Murphy KA, Church CH, Ohlfest JR, Hu P, Epstein AL. Immunogenicity of murine solid tumor models as a defining feature of in vivo behavior and response to immunotherapy. J Immunother. 2013;36(9):477-89. doi:10.1097/01.cji.0000436722.46675.4a. PMID:24145359
50. Ma W, Gilligan BM, Yuan J, Li T. Current status and perspectives in translational biomarker research for PD-1/PD-L1 immune checkpoint blockade therapy. J Hematol Oncol. 2016;9(1):47. doi:10.1186/s13045-016-0277-y. PMID:27234522
51. Wu CT, Chen WC, Chang YH, Lin WY, Chen MF. The role of PD-L1 in the radiation response and clinical outcome for bladder cancer. Sci Rep. 2016;6:19740. doi:10.1038/srep19740. PMID:26804478
52. Verbrugge I, Hagekyriakou J, Sharp LL, Galli M, West A, McLaughlin NM, Duret H, Yagita H, Johnstone RW, Smyth MJ, et al. Radiotherapy increases the permissiveness of established mammary tumors to rejection by immunomodulatory antibodies. Cancer Res. 2012;72(13):3163-74. doi:10.1158/0008-5472.CAN-12-0210. PMID:22570253
53. Demaria S, Kawashima N, Yang AM, Devitt ML, Babb JS, Allison JP, Formenti SC. Immune-mediated inhibition of metastases after treatment with local radiation and CTLA-4 blockade in a mouse model of breast cancer. Clin Cancer Res. 2005;11(2 Pt 1):728-34. doi:10.1016/j.ijrobp.2012.12.025. PMID:15701862
54. Zeng J, See AP, Phallen J, Jackson CM, Belcaid Z, Ruzevick J, Durham N, Meyer C, Harris TJ, Albesiano E, et al. Anti-PD-1 blockade and stereotactic radiation produce long-term survival in mice with intracranial gliomas. Int J Radiat Oncol Biol Phys. 2013;86(2):343-9. doi:10.1016/j.ijrobp.2012.12.025. PMID:23462419
55. Dovedi SJ, Lipowska-Bhalla G, Beers SA, Cheadle EJ, Mu L, Glennie MJ, Illidge TM, Honeychurch J. Antitumor efficacy of radiation plus immunotherapy depends upon dendritic cell activation of effector CD8+ T cells. Cancer Immunol Res. 2016;4(7):621-30. doi:10.1158/2326-6066.CIR-15-0253. PMID:27241845.
56. Fuertes MB, Kacha AK, Kline J, Woo SR, Kranz DM, Murphy KM, Gajewski TF. Host type I IFN signals are required for antitumor CD8+ T cell responses through CD8{alpha}+ dendritic cells. J Exp Med. 2011;208(10):2005-16. doi:10.1084/jem.20101159. PMID:21930765
57. Gupta A, Probst HC, Vuong V, Landshammer A, Muth S, Yagita H, Schwendener R, Pruschy M, Knuth A, van den Broek M. Radiotherapy promotes tumor-specific effector CD8+ T cells via dendritic cell activation. J Immunol. 2012;189(2):558-66. doi:10.4049/jimmunol.1200563. PMID:22685313
58. Abiko K, Matsumura N, Hamanishi J, Horikawa N, Murakami R, Yamaguchi K, Yoshioka Y, Baba T, Konishi I, Mandai M. IFN-gamma from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer. Br J Cancer. 2015;112(9):1501-9. doi:10.1038/bjc.2015.101. PMID:25867264
59. Lugade AA, Sorensen EW, Gerber SA, Moran JP, Frelinger JG, Lord EM. Radiation-induced IFN-gamma production within the tumor microenvironment influences antitumor immunity. J Immunol. 2008;180(5):3132-9. doi:10.4049/jimmunol.180.5.3132. PMID:18292536