Transformation of the tumour microenvironment by a CD40 agonist antibody correlates with improved responses to PD-L1 blockade in a mouse orthotopic pancreatic tumour model

Oncotarget

Volumn 7, Issue 14, 2016, Pages 18508-18520

  Luheshi, Nadia M ^a   Coates Ulrichsen, Jane ^a   Harper, James ^a   Mullins, Stefanie ^a   Sulikowski, Michal G ^a   Martin, Philip ^a   Brown, Lee ^a   Lewis, Arthur ^a   Davies, Gareth ^a   Morrow, Michelle ^a   Wilkinson, Robert W ^a  

^a MEDIMMUNE   (United States)

Author keywords

CD40; Microenvironment; Pancreatic cancer; PD L1

Indexed keywords

ANTINEOPLASTIC AGENT; CANCER ANTIBODY; CD40 AGONIST ANTIBODY; PROGRAMMED DEATH 1 LIGAND 1; PROGRAMMED DEATH LIGAND 1 AGONIST ANTIBODY; UNCLASSIFIED DRUG; CD274 PROTEIN, MOUSE; CD40 ANTIGEN; CTLA4 PROTEIN, MOUSE; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; MONOCLONAL ANTIBODY;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIGEN PRESENTING CELL; ARTICLE; BONE MARROW CELL; CANCER COMBINATION CHEMOTHERAPY; CD8+ T LYMPHOCYTE; CELL EXPANSION; CELL MATURATION; CHEMOSENSITIVITY; CONTROLLED STUDY; CYTOTOXIC T LYMPHOCYTE; DRUG MECHANISM; IMMUNOCOMPETENT CELL; LYMPHOCYTIC INFILTRATION; MEMORY T LYMPHOCYTE; MONOTHERAPY; MOUSE; NONHUMAN; OVERALL SURVIVAL; PANCREAS TUMOR; PHARMACOLOGICAL BLOCKING; PROTEIN EXPRESSION; SENSITIVITY ANALYSIS; TUMOR IMMUNITY; TUMOR MICROENVIRONMENT; UPREGULATION; AGONISTS; ANIMAL; ANTAGONISTS AND INHIBITORS; C57BL MOUSE; CELL TRANSFORMATION; DISEASE MODEL; FEMALE; IMMUNOLOGY; PANCREATIC NEOPLASMS; PATHOLOGY; RANDOMIZATION;

ANIMALS; ANTIBODIES, MONOCLONAL; ANTIGENS, CD274; ANTIGENS, CD40; CELL TRANSFORMATION, NEOPLASTIC; CTLA-4 ANTIGEN; DISEASE MODELS, ANIMAL; FEMALE; MICE; MICE, INBRED C57BL; PANCREATIC NEOPLASMS; RANDOM ALLOCATION; TUMOR MICROENVIRONMENT;

EID: 84975520175     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.7610     Document Type: Article

References (48)

1. Mittal D, Gubin MM, Schreiber RD and Smyth MJ. New insights into cancer immunoediting and its three component phases-elimination, equilibrium and escape. Curr Opin Immunol. 2014; 27:16-25
2. Matsushita H, Vesely MD, Koboldt DC, Rickert CG, Uppaluri R, Magrini VJ, Arthur CD, White JM, Chen YS, Shea LK, Hundal J, Wendl MC, Demeter R, Wylie T, Allison JP, Smyth MJ, et al. Cancer exome analysis reveals a T-cell-dependent mechanism of cancer immunoediting. Nature. 2012; 482:400-404
3. DuPage M, Mazumdar C, Schmidt LM, Cheung AF and Jacks T. Expression of tumour-specific antigens underlies cancer immunoediting. Nature. 2012; 482:405-409
4. Motz GT and Coukos G. Deciphering and reversing tumor immune suppression. Immunity. 2013; 39:61-73
5. Chen DS, Irving BA and Hodi FS. Molecular pathways:next-generation immunotherapy-inhibiting programmed death-ligand 1 and programmed death-1. Clin Cancer Res. 2012; 18:6580-6587
6. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012; 12:252-264
7. Sharma P and Allison JP. The future of immune checkpoint therapy. Science. 2015; 348:56-61
8. Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, Pitot HC, Hamid O, Bhatia S, Martins R, Eaton K, Chen S, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012; 366:2455-2465
9. Royal RE, Levy C, Turner K, Mathur A, Hughes M, Kammula US, Sherry RM, Topalian SL, Yang JC, Lowy I and Rosenberg SA. Phase 2 trial of single agent Ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma. J Immunother. 2010; 33:828-833
10. Taube JM, Anders RA, Young GD, Xu H, Sharma R, McMiller TL, Chen S, Klein AP, Pardoll DM, Topalian SL and Chen L. Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med. 2012; 4:127ra137
11. Taube JM, Klein A, Brahmer JR, Xu H, Pan X, Kim JH, Chen L, Pardoll DM, Topalian SL and 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; 20:5064-5074
12. Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, Chmielowski B, Spasic M, Henry G, Ciobanu V, West AN, Carmona M, Kivork C, Seja E, Cherry G, Gutierrez AJ, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014; 515:568-571
13. Clark CE, Beatty GL and Vonderheide RH. Immunosurveillance of pancreatic adenocarcinoma:insights from genetically engineered mouse models of cancer. Cancer Lett. 2009; 279:1-7
14. von Bernstorff W, Voss M, Freichel S, Schmid A, Vogel I, Johnk C, Henne-Bruns D, Kremer B and Kalthoff H. Systemic and local immunosuppression in pancreatic cancer patients. Clin Cancer Res. 2001; 7:925s-932s
15. Clark CE, Hingorani SR, Mick R, Combs C, Tuveson DA and Vonderheide RH. Dynamics of the immune reaction to pancreatic cancer from inception to invasion. Cancer Res. 2007; 67:9518-9527
16. Joyce JA and Fearon DT. T cell exclusion, immune privilege, and the tumor microenvironment. Science. 2015; 348:74-80
17. Le DT, Lutz E, Uram JN, Sugar EA, Onners B, Solt S, Zheng L, Diaz LA, Jr., Donehower RC, Jaffee EM and Laheru DA. Evaluation of ipilimumab in combination with allogeneic pancreatic tumor cells transfected with a GM-CSF gene in previously treated pancreatic cancer. J Immunother. 2013; 36:382-389
18. Lutz ER, Wu AA, Bigelow E, Sharma R, Mo G, Soares K, Solt S, Dorman A, Wamwea A, Yager A, Laheru D, Wolfgang CL, Wang J, Hruban RH, Anders RA, Jaffee EM, et al. Immunotherapy converts nonimmunogenic pancreatic tumors into immunogenic foci of immune regulation. Cancer Immunol Res. 2014; 2:616-631
19. Feig C, Jones JO, Kraman M, Wells RJ, Deonarine A, Chan DS, Connell CM, Roberts EW, Zhao Q, Caballero OL, Teichmann SA, Janowitz T, Jodrell DI, Tuveson DA and Fearon DT. Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer. Proc Natl Acad Sci U S A. 2013; 110:20212-20217
20. Zhu Y, Knolhoff BL, Meyer MA, Nywening TM, West BL, Luo J, Wang-Gillam A, Goedegebuure SP, Linehan DC and DeNardo DG. CSF1/CSF1R blockade reprograms tumorinfiltrating macrophages and improves response to T-cell checkpoint immunotherapy in pancreatic cancer models. Cancer Res. 2014; 74:5057-5069
21. Beatty GL, Torigian DA, Chiorean EG, Saboury B, Brothers A, Alavi A, Troxel AB, Sun W, Teitelbaum UR, Vonderheide RH and O'Dwyer PJ. A phase I study of an agonist CD40 monoclonal antibody (CP-870,893) in combination with gemcitabine in patients with advanced pancreatic ductal adenocarcinoma. Clin Cancer Res. 2013; 19:6286-6295
22. Elgueta R, Benson MJ, de Vries VC, Wasiuk A, Guo Y and Noelle RJ. Molecular mechanism and function of CD40/CD40L engagement in the immune system. Immunol Rev. 2009; 229:152-172
23. Vonderheide RH, Bajor DL, Winograd R, Evans RA, Bayne LJ and Beatty GL. CD40 immunotherapy for pancreatic cancer. Cancer Immunol Immunother. 2013; 62:949-954
24. Luheshi N, Davies G, Poon E, Wiggins K, McCourt M and Legg J. Th1 cytokines are more effective than Th2 cytokines at licensing anti-tumour functions in CD40-activated human macrophages in vitro. Eur J Immunol. 2014; 44:162-172
25. Beatty GL, Chiorean EG, Fishman MP, Saboury B, Teitelbaum UR, Sun W, Huhn RD, Song W, Li D, Sharp LL, Torigian DA, O'Dwyer PJ and Vonderheide RH. CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. Science. 2011; 331:1612-1616
26. Beatty GL, Winograd R, Evans RA, Long KB, Luque SL, Lee JW, Clendenin C, Gladney WL, Knoblock DM, Guirnalda PD and Vonderheide RH. Exclusion of T Cells From Pancreatic Carcinomas in Mice Is Regulated by Ly6C(low) F4/80(+) Extratumoral Macrophages. Gastroenterology. 2015; 149:201-210
27. Winograd R, Byrne KT, Evans RA, Odorizzi PM, Meyer AR, Bajor DL, Clendenin C, Stanger BZ, Furth EE, Wherry EJ and Vonderheide RH. Induction of T-cell Immunity Overcomes Complete Resistance to PD-1 and CTLA-4 Blockade and Improves Survival in Pancreatic Carcinoma. Cancer Immunol Res. 2015; 3:399-411
28. Nomi T, Sho M, Akahori T, Hamada K, Kubo A, Kanehiro H, Nakamura S, Enomoto K, Yagita H, Azuma M and Nakajima Y. Clinical significance and therapeutic potential of the programmed death-1 ligand/programmed death-1 pathway in human pancreatic cancer. Clin Cancer Res. 2007; 13:2151-2157
29. Sandin LC, Eriksson F, Ellmark P, Loskog AS, Totterman TH and Mangsbo SM. Local CTLA4 blockade effectively restrains experimental pancreatic adenocarcinoma growth in vivo. Oncoimmunology. 2014; 3:e27614
30. Vignali DA and Kuchroo VK. IL-12 family cytokines:immunological playmakers. Nat Immunol. 2012; 13:722-728
31. Becher B, Schlitzer A, Chen J, Mair F, Sumatoh HR, Teng KW, Low D, Ruedl C, Riccardi-Castagnoli P, Poidinger M, Greter M, Ginhoux F and Newell EW. High-dimensional analysis of the murine myeloid cell system. Nat Immunol. 2015; 15:1181-1189
32. Damuzzo V, Pinton L, Desantis G, Solito S, Marigo I, Bronte V and Mandruzzato S. Complexity and challenges in defining myeloid-derived suppressor cells. Cytometry B Clin Cytom. 2015; 88:77-91
33. Taylor PR, Brown GD, Geldhof AB, Martinez-Pomares L and Gordon S. Pattern recognition receptors and differentiation antigens define murine myeloid cell heterogeneity ex vivo. Eur J Immunol. 2003; 33:2090-2097
34. Zippelius A, Schreiner J, Herzig P and Muller P. Induced PD-L1 expression mediates acquired resistance to agonistic anti-CD40 treatment. Cancer Immunol Res. 2015; 3:236-244
35. Vonderheide RH and Glennie MJ. Agonistic CD40 antibodies and cancer therapy. Clin Cancer Res. 2013; 19:1035-1043
36. Marzec M, Zhang Q, Goradia A, Raghunath PN, Liu X, Paessler M, Wang HY, Wysocka M, Cheng M, Ruggeri BA and Wasik MA. Oncogenic kinase NPM/ALK induces through STAT3 expression of immunosuppressive protein CD274 (PD-L1, B7-H1). Proc Natl Acad Sci U S A. 2008; 105:20852-20857
37. Parsa AT, Waldron JS, Panner A, Crane CA, Parney IF, Barry JJ, Cachola KE, Murray JC, Tihan T, Jensen MC, Mischel PS, Stokoe D and Pieper RO. Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma. Nat Med. 2007; 13:84-88
38. Noman MZ, Desantis G, Janji B, Hasmim M, Karray S, Dessen P, Bronte V and Chouaib S. PD-L1 is a novel direct target of HIF-1alpha, and its blockade under hypoxia enhanced MDSC-mediated T cell activation. J Exp Med. 2014; 211:781-790
39. Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardiere C, Bennouna J, Bachet JB, Khemissa-Akouz F, Pere-Verge D, Delbaldo C, Assenat E, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011; 364:1817-1825
40. Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, Harris M, Reni M, Dowden S, Laheru D, Bahary N, Ramanathan RK, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013; 369:1691-1703
41. Suzuki E, Kapoor V, Jassar AS, Kaiser LR and Albelda SM. Gemcitabine selectively eliminates splenic Gr-1+/CD11b+ myeloid suppressor cells in tumor-bearing animals and enhances antitumor immune activity. Clin Cancer Res. 2005; 11:6713-6721
42. Kroemer G, Galluzzi L, Kepp O and Zitvogel L. Immunogenic cell death in cancer therapy. Annu Rev Immunol. 2013; 31:51-72
43. Homma Y, Taniguchi K, Nakazawa M, Matsuyama R, Mori R, Takeda K, Ichikawa Y, Tanaka K and Endo I. Changes in the immune cell population and cell proliferation in peripheral blood after gemcitabine-based chemotherapy for pancreatic cancer. Clin Transl Oncol. 2013; 16:330-335
44. Nowak AK, Robinson BW and Lake RA. Synergy between chemotherapy and immunotherapy in the treatment of established murine solid tumors. Cancer Res. 2003; 63:4490-4496
45. Corbett TH, Roberts BJ, Leopold WR, Peckham JC, Wilkoff LJ, Griswold DP, Jr. and Schabel FM, Jr. Induction and chemotherapeutic response of two transplantable ductal adenocarcinomas of the pancreas in C57BL/6 mice. Cancer Res. 1984; 44:717-726
46. Wang Y, Zhang Y, Yang J, Ni X, Liu S, Li Z, Hodges SE, Fisher WE, Brunicardi FC, Gibbs RA, Gingras MC and Li M. Genomic sequencing of key genes in mouse pancreatic cancer cells. Curr Mol Med. 2012; 12:331-341
47. Bruns CJ, Harbison MT, Kuniyasu H, Eue I and Fidler IJ. In vivo selection and characterization of metastatic variants from human pancreatic adenocarcinoma by using orthotopic implantation in nude mice. Neoplasia. 1999; 1:50-62
48. Elso CM, Roberts LJ, Smyth GK, Thomson RJ, Baldwin TM, Foote SJ and Handman E. Leishmaniasis host response loci (lmr1-3) modify disease severity through a Th1/Th2-independent pathway. Genes Immun. 2004; 5:93-100