PD-1 and PD-L1 blockade in gastrointestinal malignancies

Cancer Treatment Reviews

Volumn 41, Issue 10, 2015, Pages 893-903

  Lote, Hazel ^a   Cafferkey, Catherine ^a   Chau, Ian ^a  

^a ROYAL MARSDEN HOSPITAL   (United Kingdom)

Author keywords

Gastrointestinal cancer; Immune checkpoint blockade; Immunotherapy; PD 1; PD L1; Programmed death

Indexed keywords

ANGIOGENESIS INHIBITOR; ATEZOLIZUMAB; BIOLOGICAL MARKER; BMS 936559; BRUTON TYROSINE KINASE; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4 ANTIBODY; DURVALUMAB; INTERLEUKIN 2 INDUCIBLE KINASE; IPILIMUMAB; JANUS KINASE; NIVOLUMAB; PEMBROLIZUMAB; PHOSPHOTRANSFERASE; PROGRAMMED DEATH 1 LIGAND 1; PROGRAMMED DEATH 1 RECEPTOR; RAMUCIRUMAB; TICILIMUMAB; UNCLASSIFIED DRUG; ANTINEOPLASTIC AGENT; IMMUNOLOGIC FACTOR; MONOCLONAL ANTIBODY;

ADAPTIVE IMMUNITY; ADVANCED CANCER; ARTICLE; BILE DUCT CANCER; CANCER CHEMOTHERAPY; CANCER IMMUNOTHERAPY; CANCER LOCALIZATION; CANCER RADIOTHERAPY; CHEMORADIOTHERAPY; CLINICAL TRIAL (TOPIC); COLITIS; COLON ADENOCARCINOMA; COLORECTAL CANCER; DIARRHEA; DIGESTIVE SYSTEM CANCER; DISEASE ASSOCIATION; DRUG EFFICACY; DRUG SAFETY; ESOPHAGEAL ADENOCARCINOMA; ESOPHAGEAL SQUAMOUS CELL CARCINOMA; ESOPHAGUS CANCER; EVIDENCE BASED MEDICINE; GASTROINTESTINAL CARCINOMA; HUMAN; IMMUNOHISTOCHEMISTRY; INFLAMMATION; INNATE IMMUNITY; LIVER CELL CARCINOMA; LIVER DISEASE; LUNG ADENOCARCINOMA; MELANOMA; MONOTHERAPY; NON SMALL CELL LUNG CANCER; NONHUMAN; PANCREAS ADENOCARCINOMA; PANCREAS CANCER; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); SOLID TUMOR; STOMACH ADENOCARCINOMA; STOMACH CANCER; TRANSITIONAL CELL CARCINOMA; TUMOR ASSOCIATED LEUKOCYTE; TUMOR DIFFERENTIATION; ADENOCARCINOMA; ANTAGONISTS AND INHIBITORS; CELL CYCLE CHECKPOINT; COLORECTAL NEOPLASMS; ESOPHAGEAL NEOPLASMS; GASTROINTESTINAL NEOPLASMS; STOMACH NEOPLASMS;

ADENOCARCINOMA; ANTIBODIES, MONOCLONAL; ANTIBODIES, MONOCLONAL, HUMANIZED; ANTIGENS, CD274; ANTINEOPLASTIC AGENTS; CELL CYCLE CHECKPOINTS; COLORECTAL NEOPLASMS; ESOPHAGEAL NEOPLASMS; GASTROINTESTINAL NEOPLASMS; HUMANS; IMMUNOLOGIC FACTORS; PROGRAMMED CELL DEATH 1 RECEPTOR; STOMACH NEOPLASMS;

EID: 84958836241     PISSN: 03057372     EISSN: 15321967     Source Type: Journal    
DOI: 10.1016/j.ctrv.2015.09.004     Document Type: Review

References (74)

1. McDermott DF, Atkins MB. PD-1 as a potential target in cancer therapy. Cancer Med 2013;2:662-73.
2. Brahmer JR, Drake CG, Wollner I, Powderly JD, Picus J, Sharfman WH, et al. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol 2010;28:3167-75.
3. Khan MN, Wang B, Wei J, Zhang Y, Li Q, Luan X, et al. CXCR1/2 antagonism with CXCL8/Interleukin-8 analogue CXCL8(3-72)K11R/G31P restricts lung cancer growth by inhibiting tumor cell proliferation and suppressing angiogenesis. Oncotarget 2015.
4. Okudaira K, Hokari R, Tsuzuki Y, Okada Y, Komoto S, Watanabe C, et al. Blockade of B7-H1 or B7-DC induces an anti-tumor effect in a mouse pancreatic cancer model. Int J Oncol 2009;35:741-9.
5. Ausserer W. Studies of immunotherapy agents using patient-derived tumor xenografts in humanized mice. In: 2nd annual tumor models for cancer immunotherapy, Boston; 2015.
6. Liu J, Blake SJ, Smyth MJ, Teng MW. Improved mouse models to assess tumour immunity and irAEs after combination cancer immunotherapies. Clin Transl Immunol 2014;3:e22.
7. Herbst RS, Soria JC, 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.
8. Taube JM, Anders RA, Young GD, Xu H, Sharma R, McMiller TL, et al. Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med 2012;4:127ra37.
9. Lipson EJ, Sharfman WH, Drake CG, Wollner I, Taube JM, Anders RA, et al. Durable cancer regression off-treatment and effective reinduction therapy with an anti-PD-1 antibody. Clin Cancer Res 2013;19:462-8.
10. Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012;366:2443-54.
11. Patnaik A, Kang SP, Rasco D, Papadopoulos KP, Elassaiss-Schaap J, Beeram M, et al. Phase I study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in patients with advanced solid tumors. Clin Cancer Res 2015.
12. Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 2012;366:2455-65.
13. Lu J, Lee-Gabel L, Nadeau MC, Ferencz TM, Soefje SA. Clinical evaluation of compounds targeting PD-1/PD-L1 pathway for cancer immunotherapy. J Oncol Pharm Pract 2014.
14. Stewart R, Morrow M, Hammond SA, Mulgrew K, Marcus D, Poon E, et al. Identification and pre-clinical characterization of MEDI4736, an antagonistic anti-PD-L1 monoclonal antibody. Cancer Immunol Res 2015.
15. Ibrahim R, Stewart R, Shalabi A. PD-L1 blockade for cancer treatment: MEDI4736. Semin Oncol 2015;42:474-83.
16. (3rd June). .
17. Doi T, Piha-Paul SA, Ibrahim Jalal S, Mai-Dang H, Yuan S, Koshiji M, et al. Pembrolizumab (MK-3475) for patients (pts) with advanced esophageal carcinoma: preliminary results from KEYNOTE-028. Presented at the ASCO annual meeting; 2015.
18. Network CGAR. Comprehensive molecular characterization of gastric adenocarcinoma. Nature 2014;513:202-9.
19. Muro K, Bang Y, Shankaran V, Geva R, Catenacci D, Gupta S, et al. LBA15A phase 1B study of pembrolizumab (Pembro; MK-3475) in patients (Pts) with advanced gastric cancer. Ann Oncol 2014;25(Suppl. 4).
20. Muro K, Bang Y-J, Shankaran V, Geva R, Catenacci DVT, Gupta S, et al. Relationship between PD-L1 expression and clinical outcomes in patients (Pts) with advanced gastric cancer treated with the anti-PD-1 monoclonal antibody pembrolizumab (Pembro; MK-3475) in KEYNOTE-012. Presented at the ASCO 2015 gastrointestinal cancers symposium; 2015.
21. Shankaran V, Muro K, Bang Y-J, Geva R, Catenacci D, Gupta S, et al. Correlation of gene expression signatures and clinical outcomes in patients with advanced gastric cancer treated with pembrolizumab (MK-3475). J Clin Oncol 2015;33.
22. Bang Y, et al. Clinical outcomes and their correlation with gene expression in patients with advanced gastric cancer treatment with pembrolizumab (MK-3475): KEYNOTE-012. Presented at the ESMO 17th world congress on gastrointestinal cancer; 2015.
23. Gulley ML. Genomic assays for Epstein-Barr virus-positive gastric adenocarcinoma. Exp Mol Med 2015;47:e134.
24. Constanza Camargo M, Bowlby R, Chu A, Pedamallu CS, Thorsson V, Elmore S, et al. Validation and calibration of next-generation sequencing to identify Epstein-Barr virus-positive gastric cancer in The Cancer Genome Atlas. Gastric Cancer 2015.
25. Partlová S, Bouček J, Kloudová K, Lukešová E, Zábrodský M, Grega M, et al. Distinct patterns of intratumoral immune cell infiltrates in patients with HPVassociated compared to non-virally induced head and neck squamous cell carcinoma. Oncoimmunology 2015;4:e965570.
26. Kondo Y, Kimura O, Tanaka Y, Ninomiya M, Iwata T, Kogure T, et al. Differential expression of CX3CL1 in hepatitis B virus-replicating hepatoma cells can affect the migration activity of CX3CR1+ immune cells. J Virol 2015;89: 7016-27.
27. Li X, Gao C, Yang Y, Zhou F, Li M, Jin Q, et al. Systematic review with metaanalysis: the association between human papillomavirus infection and oesophageal cancer. Aliment Pharmacol Ther 2014;39:270-81.
28. C. Verslype C, Rosmorduc O, Rougier P, Group EGW. Hepatocellular carcinoma: ESMO-ESDO clinical practice guidelines for diagnosis, treatment and followup. Ann Oncol 2012;23(Suppl. 7):vii41-8.
29. Gehring AJ, Ho ZZ, Tan AT, Aung MO, Lee KH, Tan KC, et al. Profile of tumor antigen-specific CD8 T cells in patients with hepatitis B virus-related hepatocellular carcinoma. Gastroenterology 2009;137:682-90.
30. El-Khoueiry A, Melero I, Crocenzi T, Welling T, Yau T, Yeo W, et al. Presented at the ASCO; 2015.
31. Royal RE, Levy C, Turner K, Mathur A, Hughes M, Kammula US, et al. Phase 2 trial of single agent Ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma. J Immunother 2010;33:828-33.
32. (10th April). Available: .
33. Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 2015.
34. Llosa NJ, Cruise M, Tam A, Wicks EC, Hechenbleikner EM, Taube JM, et al. The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints. Cancer Discov 2015;5: 43-51.
35. Sadanandam A, Lyssiotis CA, Homicsko K, Collisson EA, Gibb WJ, Wullschleger S, et al. A colorectal cancer classification system that associates cellular phenotype and responses to therapy. Nat Med 2013;19:619-25.
36. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, et al. Combined nivolumab and Ipilimumab or monotherapy in untreated melanoma. N Engl J Med 2015;373:23-34.
37. Wang BJ, Bao JJ, Wang JZ, Wang Y, Jiang M, Xing MY, et al. Immunostaining of PD-1/PD-Ls in liver tissues of patients with hepatitis and hepatocellular carcinoma. World J Gastroenterol 2011;17:3322-9.
38. Bigelow E, Bever KM, Xu H, Yager A, Wu A, Taube J, et al. Immunohistochemical staining of B7-H1 (PD-L1) on paraffin-embedded slides of pancreatic adenocarcinoma tissue. J Vis Exp 2013.
39. Loos M, Giese NA, Kleeff J, Giese T, Gaida MM, Bergmann F, et al. Clinical significance and regulation of the costimulatory molecule B7-H1 in pancreatic cancer. Cancer Lett 2008;268:98-109.
40. Song X, Liu J, Lu Y, Jin H, Huang D. Overexpression of B7-H1 correlates with malignant cell proliferation in pancreatic cancer. Oncol Rep 2014;31:1191-8.
41. Ye Y, Zhou L, Xie X, Jiang G, Xie H, Zheng S. Interaction of B7-H1 on intrahepatic cholangiocarcinoma cells with PD-1 on tumor-infiltrating T cells as a mechanism of immune evasion. J Surg Oncol 2009;100:500-4.
42. Ohigashi Y, Sho M, Yamada Y, Tsurui Y, Hamada K, Ikeda N, et al. Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand-2 expression in human esophageal cancer. Clin Cancer Res 2005;11:2947-53.
43. Suleiman Y, Coppola D, Zibadi S, Dalia S, Juan T, Lee JK, et al. Prognostic value of tumor-infiltrating lymphocytes (TILs) and expression of PD-L1 in cholangiocarcinoma. Presented at the gastrointestinal cancers symposium; 2015.
44. Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA, Lesokhin AM, et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med 2013;369:122-33.
45. Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 2015;348:124-8.
46. Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WE, Poddubskaya E, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med 2015.
47. Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, et al. Tumorassociated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 2002;8:793-800.
48. Hoffman J. Pembrolizumab shows antitumor activity, manageable toxicity in advanced gastric cancer; 2015. Available: .
49. Muro K, Bang YJ, Shankaran V, et al. Relationship between PD-L1 expression and clinical outcomes in patients (Pts) with advanced gastric cancer treated with the anti-PD-1 monoclonal antibody pembrolizumab (Pembro; MK-3475) in KEYNOTE-012; 2015.
50. Patel SP, Kurzrock R. PD-L1 expression as a predictive biomarker in cancer immunotherapy. Mol Cancer Ther 2015;14:847-56.
51. Muro K, Bang Y, Shanharan V, Geva R, Catenacci D, Gupta S, et al. LBA15 - A phase 1b study of pembrolizumab (Pembro; MK-3475) in patients (Pts) with advanced gastric cancer; 2014.
52. Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 2014;515:568-71.
53. Smyrk TC, Watson P, Kaul K, Lynch HT. Tumor-infiltrating lymphocytes are a marker for microsatellite instability in colorectal carcinoma. Cancer 2001;91:2417-22.
54. Mihm MC, Mulé JJ. Reflections on the histopathology of tumor-infiltrating lymphocytes in melanoma and the host immune response. Cancer Immunol Res 2015;3:827-35.
55. Sierro S, Romero P, Speiser DE. The CD4-like molecule LAG-3, biology and therapeutic applications. Expert Opin Ther Targets 2011;15:91-101.
56. Woo SR, Turnis ME, Goldberg MV, Bankoti J, Selby M, Nirschl CJ, et al. Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer Res 2012;72:917-27.
57. Bartkowiak T, Curran MA. 4-1BB agonists: multi-potent potentiators of tumor immunity. Front Oncol 2015;5:117.
58. Jacobs J, Deschoolmeester V, Zwaenepoel K, Rolfo C, Silence K, Rottey S, et al. CD70: an emerging target in cancer immunotherapy. Pharmacol Ther 2015.
59. Kim YJ. Subverting the adaptive immune resistance mechanism to improve clinical responses to immune checkpoint blockade therapy. Oncoimmunology 2014;3:e954868.
60. Zhao BG, Vasilakos JP, Tross D, Smirnov D, Klinman DM. Combination therapy targeting toll like receptors 7, 8 and 9 eliminates large established tumors. J Immunother Cancer 2014;2:12.
61. Lu H. TLR agonists for cancer immunotherapy: tipping the balance between the immune stimulatory and inhibitory effects. Front Immunol 2014;5:83.
62. Scala S. Molecular pathways: targeting the CXCR4-CXCL12 axis-untapped potential in the tumor microenvironment. Clin Cancer Res 2015.
63. Sharma B, Singh S, Varney ML, Singh RK. Targeting CXCR1/CXCR2 receptor antagonism in malignant melanoma. Expert Opin Ther Targets 2010;14: 435-42.
64. Reck M, Paz-Ares L. Immunologic checkpoint blockade in lung cancer. Semin Oncol 2015;42:402-17.
65. Carrega P, Morandi B, Costa R, Frumento G, Forte G, Altavilla G, et al. Natural killer cells infiltrating human nonsmall-cell lung cancer are enriched in CD56 bright CD16(-) cells and display an impaired capability to kill tumor cells. Cancer 2008;112:863-75.
66. Huang Y, Yuan J, Righi E, Kamoun WS, Ancukiewicz M, Nezivar J, et al. Vascular normalizing doses of antiangiogenic treatment reprogram the immunosuppressive tumor microenvironment and enhance immunotherapy. Proc Natl Acad Sci USA 2012;109:17561-6.
67. Yasuda S, Sho M, Yamato I, Yoshiji H, Wakatsuki K, Nishiwada S, et al. Simultaneous blockade of programmed death 1 and vascular endothelial growth factor receptor 2 (VEGFR2) induces synergistic anti-tumour effect in vivo. Clin Exp Immunol 2013;172:500-6.
68. Bellucci R, Martin A, Bommarito D, Wang K, Hansen SH, Freeman GJ, et al. Interferon-c-induced activation of JAK1 and JAK2 suppresses tumor cell susceptibility to NK cells through upregulation of PD-L1 expression. Oncoimmunology 2015;4:e1008824.
69. Sagiv-Barfi I, Kohrt HE, Czerwinski DK, Ng PP, Chang BY, Levy R. Therapeutic antitumor immunity by checkpoint blockade is enhanced by ibrutinib, an inhibitor of both BTK and ITK. Proc Natl Acad Sci USA 2015;112:E966-72.
70. clinicaltrials.gov. (September 10).
71. Teng F, Kong L, Meng X, Yang J, Yu J. Radiotherapy combined with immune checkpoint blockade immunotherapy: achievements and challenges. Cancer Lett 2015;365:23-9.
72. 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.
73. Stagg J, Loi S, Divisekera U, Ngiow SF, Duret H, Yagita H, et al. Anti-ErbB-2 mAb therapy requires type I and II interferons and synergizes with anti-PD-1 or anti-CD137 mAb therapy. Proc Natl Acad Sci USA 2011;108:7142-7.
74. Park S, Jiang Z, Mortenson ED, Deng L, Radkevich-Brown O, Yang X, et al. The therapeutic effect of anti-HER2/neu antibody depends on both innate and adaptive immunity. Cancer Cell 2010;18:160-70.