Integrative analysis identifies a novel AXL-PI3 kinase-PD-L1 signaling axis associated with radiation resistance in head and neck cancer

Clinical Cancer Research

Volumn 23, Issue 11, 2017, Pages 2713-2722

  Skinner, Heath D ^a   Giri, Uma ^a   Yang, Liang P ^b   Kumar, Manish ^b   Liu, Ying ^b   Story, Michael D ^c   Pickering, Curtis R ^a   Byers, Lauren A ^a   Williams, Michelle D ^a   Wang, Jing ^a   Shen, Li ^a   Yoo, Suk Y ^a   Fan, You Hong ^a   Molkentine, David P ^b   Beadle, Beth M ^a   Meyn, Raymond E ^b   Myers, Jeffrey N ^a   Heymach, John V ^a  

^a UNIVERSITY OF TEXAS   (United States)

^b UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^c UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MESSENGER RNA; ONCOPROTEIN; PHOSPHATIDYLINOSITOL 3 KINASE; PROGRAMMED DEATH 1 LIGAND 1; PROTEIN AXL; UNCLASSIFIED DRUG; AXL RECEPTOR TYROSINE KINASE; CD274 PROTEIN, HUMAN; PROTEIN TYROSINE KINASE; TUMOR MARKER;

ARTICLE; CD8+ T LYMPHOCYTE; COHORT ANALYSIS; CONTROLLED STUDY; DOWN REGULATION; ENZYME ACTIVATION; GENOME ANALYSIS; HEAD AND NECK SQUAMOUS CELL CARCINOMA; HUMAN; HUMAN CELL; IMMUNOHISTOCHEMISTRY; IMMUNOMODULATION; IN VITRO STUDY; MAJOR CLINICAL STUDY; OUTCOME ASSESSMENT; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEOMICS; RADIATION EXPOSURE; RADIOSENSITIVITY; SIGNAL TRANSDUCTION; SQUAMOUS CELL CARCINOMA CELL LINE; TRANSCRIPTOMICS; TREATMENT FAILURE; UPREGULATION; AGED; FEMALE; GENE EXPRESSION REGULATION; GENETICS; HEAD AND NECK TUMOR; MALE; MIDDLE AGED; PAPILLOMAVIRIDAE; PATHOGENICITY; PATHOLOGY; RADIATION RESPONSE; RADIATION TOLERANCE; SQUAMOUS CELL CARCINOMA; TUMOR ASSOCIATED LEUKOCYTE; TUMOR CELL LINE;

AGED; B7-H1 ANTIGEN; BIOMARKERS, TUMOR; CARCINOMA, SQUAMOUS CELL; CELL LINE, TUMOR; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; HEAD AND NECK NEOPLASMS; HUMANS; LYMPHOCYTES, TUMOR-INFILTRATING; MALE; MIDDLE AGED; PAPILLOMAVIRIDAE; PHOSPHATIDYLINOSITOL 3-KINASES; PROTEOMICS; PROTO-ONCOGENE PROTEINS; RADIATION TOLERANCE; RECEPTOR PROTEIN-TYROSINE KINASES; RNA, MESSENGER; SIGNAL TRANSDUCTION;

EID: 85020269576     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-16-2586     Document Type: Article

References (40)

1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015;65:87-108.
2. Ang KK, Zhang Q, Rosenthal DI, Nguyen-Tan PF, Sherman EJ, Weber RS, et al. Randomized phase III trial of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III to IV head and neck carcinoma: RTOG 0522. J Clin Oncol 2014;32:2940-50.
3. Harari PM, Harris J, Kies MS, Myers JN, Jordan RC, Gillison ML, et al. Postoperative chemoradiotherapy and cetuximab for high-risk squamous cell carcinoma of the head and neck: Radiation Therapy Oncology Group RTOG-0234. JCO 2014;32:2486-95.
4. Nguyen-Tan PF, Zhang Q, Ang KK, Weber RS, Rosenthal DI, Soulieres D, et al. Randomized phase III trial to test accelerated versus standard fractionation in combination with concurrent cisplatin for head and neck carcinomas in the Radiation Therapy Oncology Group 0129 Trial: Long-Term Report of Efficacy and Toxicity. JCO 2014;32:3858-67.
5. Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tan PF, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 2010;363:24-35.
6. Brand TM, Iida M, Stein AP, Corrigan KL, Braverman CM, Coan JP, et al. AXL is a logical molecular target in head and neck squamous cell carcinoma. Clin Cancer Res 2015;21:2601-12.
7. Bussink J, van der Kogel AJ, Kaanders JHAM. Activation of the PI3-K/AKT pathway and implications for radioresistance mechanisms in head and neck cancer. Lancet Oncol 2008;9:288-96.
8. Skinner HD, Giri U, Yang L, Woo SH, Story MD, Pickering CR, et al. Proteomic profiling identifies PTK2/FAK as a driver of radioresistance in HPV negative head and neck cancer. Clin Cancer Res 2016;22:4643-50.
9. Reits EA, Hodge JW, Herberts CA, Groothuis TA, Chakraborty M, K. Wansley E, et al. Radiation modulates the peptide repertoire, enhances MHCclass I expression, and induces successful antitumorimmunotherapy. J Exp Med 2006;203:1259-71.
10. 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;174:7516-23.
11. Lee Y, Auh SL, Wang Y, Burnette B, Wang Y, Meng Y, et al. Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment. Blood 2009;114:589-95.
12. Deng L, Liang H, Burnette B, Beckett M, Darga T, Weichselbaum RR, et al. Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice. J Clin Invest 2014;124:687-95.
13. Peng W, Chen JQ, Liu C, Malu S, Creasy C, Tetzlaff MT, et al. Loss of PTEN promotes resistance to T cell-mediated immunotherapy. Cancer Discov 2016;6:202-16.
14. Lou Y, Diao L, Parra Cuentas ER, Denning WL, Chen L, Fan YH, et al. Epithelial-mesenchymal transition is associated with a distinct tumor microenvironment including elevation of inflammatory signals and multiple immune checkpoints in lung adenocarcinoma. Clin Cancer Res 2016;22:3630-42.
15. Ock C-Y, Kim S, Keam B, Kim M, Kim TM, Kim J-H, et al. PD-L1 expression is associated with epithelial-mesenchymal transition in head and neck squamous cell carcinoma. Oncotarget 2016;7:15901-14.
16. Byers LA, Diao L, Wang J, Saintigny P, Girard L, Peyton M, et al. An epithelial-mesenchymal transition gene signature predicts resistance to EGFR and PI3K inhibitors and identifies Axl as a therapeutic target for overcoming EGFR inhibitor resistance. Clin Cancer Res 2013;19:279-90.
17. Yang Y, Ahn Y-H, Chen Y, Tan X, Guo L, Gibbons DL, et al. ZEB1 sensitizes lung adenocarcinoma to metastasis suppression by PI3K antagonism. J Clin Invest 2014;124:2696-708.
18. Marie-Egyptienne DT, Lohse I, Hill RP. Cancer stem cells, the epithelial to mesenchymal transition (EMT) and radioresistance: potential role of hypoxia. Cancer Lett 2013;341:63-72.
19. Skoulidis F, Byers LA, Diao L, Papadimitrakopoulou VA, Tong P, Izzo J, et al. Co-occurring genomic alterations define major subsets of KRASmutant lung adenocarcinoma with distinct biology, immune profiles, and therapeutic vulnerabilities. Cancer Discov 2015;5:860-77.
20. Byers LA, Wang J, Nilsson MB, Fujimoto J, Saintigny P, Yordy J, et al. Proteomic profiling identifies dysregulated pathways in small cell lung cancer and novel therapeutic targets including PARP1. Cancer Discov 2012;2:798-811.
21. The Cancer Genome Atlas Network. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature 2015;517:576-82.
22. Moeller BJ, Yordy JS, Williams MD, Giri U, Raju U, Molkentine DP, et al. DNA repair biomarker profiling of head and neck cancer: Ku80 expression predicts locoregional failure and death following radiotherapy. Clin Cancer Res 2011;17:2035-43.
23. Herbst RS, Soria J-C, Kowanetz M, Fine GD, Hamid O, Gordon MS, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 2014;515:563-7.
24. Powles T, Eder JP, Fine GD, Braiteh FS, Loriot Y, Cruz C, et al. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature 2014;515:558-62.
25. Rosenblatt J, Glotzbecker B, Mills H, Vasir B, Tzachanis D, Levine JD, et al. PD-1 blockade by CT-011, anti-PD-1 antibody, enhances ex vivo T-cell responses to autologous dendritic cell/myeloma fusion vaccine. J Immunother 2011;34:409-18.
26. Poeta ML, Manola J, Goldwasser MA, Forastiere A, Benoit N, Califano JA, et al. TP53 mutations and survival in squamous-cell carcinoma of the head and neck. N Engl J Med 2007;357:2552-61.
27. Skinner HD, Sandulache VC, Ow TJ, Meyn RE, Yordy JS, Beadle BM, et al. TP53 disruptive mutations lead to head and neck cancer treatment failure through inhibition of radiation-induced senescence. Clin Cancer Res 2012;18:290-300.
28. Concha-Benavente F, Srivastava RM, Trivedi S, Lei Y, Chandran U, Seethala RR, et al. Identification of the cell-intrinsic and -extrinsic pathways downstream of EGFR and IFNg that induce PD-L1 expression in head and neck cancer. Cancer Res 2016;76:1031-43.
29. Mak MP, Tong P, Diao L, Cardnell RJ, Gibbons DL, William WN, et al. A patient-derived, pan-cancer EMT signature identifies global molecular alterations and immune target enrichment following epithelial-to-mesenchymal transition. Clin Cancer Res 2016;22:609-20.
30. Hugo W, Zaretsky JM, Sun L, Song C, Moreno BH, Hu-Lieskovan S, et al. Genomic and transcriptomic features of response to anti-PD-1 therapy in metastatic melanoma. Cell 2016;165:35-44.
31. Dufies M, Jacquel A, Belhacene N, Robert G, Cluzeau T, Luciano F, et al. Mechanisms of AXL overexpression and function in Imatinib-resistant chronic myeloid leukemia cells. Oncotarget 2011;2:874-85.
32. Atefi M, Avramis E, Lassen A, Wong DJL, Robert L, Foulad D, et al. Effects of MAPK and PI3K pathways on PD-L1 expression in melanoma. Clin Cancer Res 2014;20:3446-57.
33. Shi F, Shi M, Zeng Z, Qi R-Z, Liu Z-W, Zhang J-Y, et al. PD-1 and PD-L1 upregulation promotes CD8 (+) T-cell apoptosis and postoperative recurrence in hepatocellular carcinoma patients. Int J Cancer 2011;128:887-96.
34. Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJM, Robert L, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 2014;515:568-71.
35. Sfanos KS, Bruno TC, Meeker AK, De Marzo AM, Isaacs WB, Drake CG. Human prostate-infiltrating CD8+ T lymphocytes are oligoclonal and PD-1+. Prostate 2009;69:1694-703.
36. Ahmadzadeh M, Johnson LA, Heemskerk B, Wunderlich JR, Dudley ME, White DE, et al. Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired. Blood 2009;114:1537-44.
37. Lee S-J, Jang B-C, Lee S-W, Yang Y-I, Suh S-I, Park Y-M, et al. Interferon regulatory factor-1 is prerequisite to the constitutive expression and IFNgammainduced upregulation of B7-H1 (CD274). FEBS Lett 2006;580:755-62.
38. Abiko K, Matsumura N, Hamanishi J, Horikawa N, Murakami R, Yamaguchi K, et al. IFN-g from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer. Br J Cancer 2015;112:1501-9.
39. Day CL, Kaufmann DE, Kiepiela P, Brown JA, Moodley ES, Reddy S, et al. PD-1 expression onHIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature 2006;443:350-4.
40. Wherry EJ. T cell exhaustion. Nat Immunol 2011;12:492-9.