1. Ottaviano M, De Placido S, Ascierto PA. Recent success and limitations of immune checkpoint inhibitors for cancer: a lesson from melanoma. Virchows Arch 2019;474(4):421-32. doi: 10.1007/s00428-019-02538-4 [published Online First: 2019/02/13]
2. Tan E, El-Rayes B. Pancreatic Cancer and Immunotherapy: Resistance Mechanisms and Proposed Solutions. J Gastrointest Cancer 2019;50(1):1-8. doi: 10.1007/s12029-018-0179-z [published Online First: 2018/11/18]
3. Blando J, Sharma A, Higa MG, et al. Comparison of immune infiltrates in melanoma and pancreatic cancer highlights VISTA as a potential target in pancreatic cancer. Proc Natl Acad Sci U S A 2019;116(5):1692-97. doi: 10.1073/pnas.1811067116 [published Online First: 2019/01/13]
4. Ene-Obong A, Clear AJ, Watt J, et al. Activated pancreatic stellate cells sequester CD8+ T cells to reduce their infiltration of the juxtatumoral compartment of pancreatic ductal adenocarcinoma. Gastroenterology 2013;145(5):1121-32. doi: 10.1053/j.gastro.2013.07.025 [published Online First: 2013/07/31]
5. Gorchs L, Fernandez Moro C, Bankhead P, et al. Human Pancreatic Carcinoma-Associated Fibroblasts Promote Expression of Co-inhibitory Markers on CD4(+) and CD8(+) T-Cells. Front Immunol 2019;10:847. doi: 10.3389/fimmu.2019.00847 [published Online First: 2019/05/10]
6. Lakins MA, Ghorani E, Munir H, et al. Cancer-associated fibroblasts induce antigen-specific deletion of CD8 (+) T Cells to protect tumour cells. Nat Commun 2018;9(1):948. doi: 10.1038/s41467-018-03347-0 [published Online First: 2018/03/07]
7. Feig C, Jones JO, Kraman M, et al. 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(50):20212-7. doi: 10.1073/pnas.1320318110 [published Online First: 2013/11/28]
8. Farren MR, Mace TA, Geyer S, et al. Systemic Immune Activity Predicts Overall Survival in Treatment-Naive Patients with Metastatic Pancreatic Cancer. Clin Cancer Res 2016;22(10):2565-74. doi: 10.1158/1078-0432.CCR-15-1732 [published Online First: 2016/01/01]
9. Dienz O, Rincon M. The effects of IL-6 on CD4 T cell responses. Clin Immunol 2009;130(1):27-33. doi: 10.1016/j.clim.2008.08.018 [published Online First: 2008/10/11]
10. Liu Q, Yu S, Li A, et al. Targeting interlukin-6 to relieve immunosuppression in tumor microenvironment. Tumour Biol 2017;39(6):1010428317712445. doi: 10.1177/1010428317712445 [published Online First: 2017/06/24]
11. Boj SF, Hwang CI, Baker LA, et al. Organoid models of human and mouse ductal pancreatic cancer. Cell 2015;160(1-2):324-38. doi: 10.1016/j.cell.2014.12.021 [published Online First: 2015/01/06]
12. Chen H, Liakou CI, Kamat A, et al. Anti-CTLA-4 therapy results in higher CD4+ICOShi T cell frequency and IFN-gamma levels in both nonmalignant and malignant prostate tissues. Proc Natl Acad Sci U S A 2009;106(8):2729-34. doi: 10.1073/pnas.0813175106 [published Online First: 2009/02/10]
13. Liakou CI, Kamat A, Tang DN, et al. CTLA-4 blockade increases IFNgamma-producing CD4+ICOShi cells to shift the ratio of effector to regulatory T cells in cancer patients. Proc Natl Acad Sci U S A 2008;105(39):14987-92. doi: 10.1073/pnas.0806075105 [published Online First: 2008/09/27]
14. Bengsch F, Knoblock DM, Liu A, et al. CTLA-4/CD80 pathway regulates T cell infiltration into pancreatic cancer. Cancer Immunol Immunother 2017;66(12):1609-17. doi: 10.1007/s00262-017-2053-4 [published Online First: 2017/09/01]
15. Diehl S, Chow CW, Weiss L, et al. Induction of NFATc2 expression by interleukin 6 promotes T helper type 2 differentiation. J Exp Med 2002;196(1):39-49. doi: 10.1084/jem.20020026 [published Online First: 2002/07/03]
16. Diehl S, Rincon M. The two faces of IL-6 on Th1/Th2 differentiation. Mol Immunol 2002;39(9):531-6. doi: 10.1016/s0161-5890(02)00210-9 [published Online First: 2002/11/15]
17. Rincon M, Anguita J, Nakamura T, et al. Interleukin (IL)-6 directs the differentiation of IL-4-producing CD4+ T cells. J Exp Med 1997;185(3):461-9. doi: 10.1084/jem.185.3.461 [published Online First: 1997/02/03]
18. Oosterwegel MA, Mandelbrot DA, Boyd SD, et al. The role of CTLA-4 in regulating Th2 differentiation. J Immunol 1999;163(5):2634-9. [published Online First: 1999/08/24]
19. Paterson AM, Lovitch SB, Sage PT, et al. Deletion of CTLA-4 on regulatory T cells during adulthood leads to resistance to autoimmunity. J Exp Med 2015;212(10):1603-21. doi: 10.1084/jem.20141030 [published Online First: 2015/09/16]
20. Mace TA, Ameen Z, Collins A, et al. Pancreatic cancer-associated stellate cells promote differentiation of myeloid-derived suppressor cells in a STAT3-dependent manner. Cancer Res 2013;73(10):3007-18. doi: 10.1158/0008-5472.can-12-4601 [published Online First: 2013/03/22]
21. McLoughlin RM, Jenkins BJ, Grail D, et al. IL-6 trans-signaling via STAT3 directs T cell infiltration in acute inflammation. Proc Natl Acad Sci U S A 2005;102(27):9589-94. doi: 10.1073/pnas.0501794102 [published Online First: 2005/06/25]
22. Loetscher M, Gerber B, Loetscher P, et al. Chemokine receptor specific for IP10 and mig: structure, function, and expression in activated T-lymphocytes. J Exp Med 1996;184(3):963-9. doi: 10.1084/jem.184.3.963 [published Online First: 1996/09/01]
23. Loetscher M, Loetscher P, Brass N, et al. Lymphocyte-specific chemokine receptor CXCR3: regulation, chemokine binding and gene localization. Eur J Immunol 1998;28(11):3696-705. doi: 10.1002/(SICI)1521-4141(199811)28:11<3696::AID-IMMU3696>3.0.CO;2-W [published Online First: 1998/12/08]
24. Cole KE, Strick CA, Paradis TJ, et al. Interferon-inducible T cell alpha chemoattractant (I-TAC): a novel non-ELR CXC chemokine with potent activity on activated T cells through selective high affinity binding to CXCR3. J Exp Med 1998;187(12):2009-21. doi: 10.1084/jem.187.12.2009 [published Online First: 1998/06/24]
25. Lu B, Humbles A, Bota D, et al. Structure and function of the murine chemokine receptor CXCR3. Eur J Immunol 1999;29(11):3804-12. doi: 10.1002/(SICI)1521-4141(199911)29:11<3804::AID-IMMU3804>3.0.CO;2-9 [published Online First: 1999/11/11]
26. Mace TA, Shakya R, Pitarresi JR, et al. IL-6 and PD-L1 antibody blockade combination therapy reduces tumour progression in murine models of pancreatic cancer. Gut 2016 doi: 10.1136/gutjnl-2016-311585 [published Online First: 2016/11/01]
27. Angevin E, Tabernero J, Elez E, et al. A phase I/II, multiple-dose, dose-escalation study of siltuximab, an anti-interleukin-6 monoclonal antibody, in patients with advanced solid tumors. Clin Cancer Res 2014;20(8):2192-204. doi: 10.1158/1078-0432.CCR-13-2200 [published Online First: 2014/02/25]
28. Kamath SD, Kalyan A, Kircher S, et al. Ipilimumab and Gemcitabine for Advanced Pancreatic Cancer: A Phase Ib Study. Oncologist 2019 doi: 10.1634/theoncologist.2019-0473 [published Online First: 2019/11/20]
29. Royal RE, Levy C, Turner K, et al. Phase 2 trial of single agent Ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma. J Immunother 2010;33(8):828-33. doi: 10.1097/CJI.0b013e3181eec14c [published Online First: 2010/09/16]
30. Lamano JB, Lamano JB, Li YD, et al. Glioblastoma-Derived IL6 Induces Immunosuppressive Peripheral Myeloid Cell PD-L1 and Promotes Tumor Growth. Clin Cancer Res 2019;25(12):3643-57. doi: 10.1158/1078-0432.CCR-18-2402 [published Online First: 2019/03/03]
31. Li J, Xu J, Yan X, et al. Targeting Interleukin-6 (IL-6) Sensitizes Anti-PD-L1 Treatment in a Colorectal Cancer Preclinical Model. Med Sci Monit 2018;24:5501-08. doi: 10.12659/MSM.907439 [published Online First: 2018/08/09]
32. Tsukamoto H, Fujieda K, Miyashita A, et al. Combined Blockade of IL6 and PD-1/PD-L1 Signaling Abrogates Mutual Regulation of Their Immunosuppressive Effects in the Tumor Microenvironment. Cancer Res 2018;78(17):5011-22. doi: 10.1158/0008-5472.CAN-18-0118 [published Online First: 2018/07/04]
33. Biffi G, Oni TE, Spielman B, et al. IL1-Induced JAK/STAT Signaling Is Antagonized by TGFbeta to Shape CAF Heterogeneity in Pancreatic Ductal Adenocarcinoma. Cancer Discov 2019;9(2):282-301. doi: 10.1158/2159-8290.CD-18-0710 [published Online First: 2018/10/28]
34. Ohlund D, Handly-Santana A, Biffi G, et al. Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer. J Exp Med 2017;214(3):579-96. doi: 10.1084/jem.20162024 [published Online First: 2017/02/25]
35. Jang JE, Hajdu CH, Liot C, et al. Crosstalk between Regulatory T Cells and Tumor-Associated Dendritic Cells Negates Anti-tumor Immunity in Pancreatic Cancer. Cell Rep 2017;20(3):558-71. doi: 10.1016/j.celrep.2017.06.062 [published Online First: 2017/07/21]
36. Alspach E, Lussier DM, Miceli AP, et al. MHC-II neoantigens shape tumour immunity and response to immunotherapy. Nature 2019;574(7780):696-701. doi: 10.1038/s41586-019-1671-8 [published Online First: 2019/10/28]
37. Dunn GP, Koebel CM, Schreiber RD. Interferons, immunity and cancer immunoediting. Nat Rev Immunol 2006;6(11):836-48. doi: 10.1038/nri1961 [published Online First: 2006/10/26]
38. Ikeda H, Old LJ, Schreiber RD. The roles of IFN gamma in protection against tumor development and cancer immunoediting. Cytokine Growth Factor Rev 2002;13(2):95-109. doi: 10.1016/s1359-6101(01)00038-7 [published Online First: 2002/03/20]
39. Detjen KM, Farwig K, Welzel M, et al. Interferon gamma inhibits growth of human pancreatic carcinoma cells via caspase-1 dependent induction of apoptosis. Gut 2001;49(2):251-62. doi: 10.1136/gut.49.2.251 [published Online First: 2001/07/17]
40. Chin YE, Kitagawa M, Kuida K, et al. Activation of the STAT signaling pathway can cause expression of caspase 1 and apoptosis. Mol Cell Biol 1997;17(9):5328-37. doi: 10.1128/mcb.17.9.5328 [published Online First: 1997/09/01]
41. Gao J, Shi LZ, Zhao H, et al. Loss of IFN-gamma Pathway Genes in Tumor Cells as a Mechanism of Resistance to Anti-CTLA-4 Therapy. Cell 2016;167(2):397-404 e9. doi: 10.1016/j.cell.2016.08.069 [published Online First: 2016/09/27]
42. Chow MT, Ozga AJ, Servis RL, et al. Intratumoral Activity of the CXCR3 Chemokine System Is Required for the Efficacy of Anti-PD-1 Therapy. Immunity 2019;50(6):1498-512 e5. doi: 10.1016/j.immuni.2019.04.010 [published Online First: 2019/05/18]
43. Uemura M, Trinh VA, Haymaker C, et al. Selective inhibition of autoimmune exacerbation while preserving the anti-tumor clinical benefit using IL-6 blockade in a patient with advanced melanoma and Crohn's disease: a case report. J Hematol Oncol 2016;9(1):81. doi: 10.1186/s13045-016-0309-7 [published Online First: 2016/09/07]
44. Maude SL, Barrett D, Teachey DT, et al. Managing cytokine release syndrome associated with novel T cell-engaging therapies. Cancer J 2014;20(2):119-22. doi: 10.1097/PPO.0000000000000035 [published Online First: 2014/03/29]
45. Horisberger A, La Rosa S, Zurcher JP, et al. A severe case of refractory esophageal stenosis induced by nivolumab and responding to tocilizumab therapy. J Immunother Cancer 2018;6(1):156. doi: 10.1186/s40425-018-0481-0 [published Online First: 2018/12/28]
46. Bankhead P, Loughrey MB, Fernandez JA, et al. QuPath: Open source software for digital pathology image analysis. Sci Rep 2017;7(1):16878. doi: 10.1038/s41598-017-17204-5 [published Online First: 2017/12/06]
47. Muranski P, Boni A, Antony PA, et al. Tumor-specific Th17-polarized cells eradicate large established melanoma. Blood 2008;112(2):362-73. doi: 10.1182/blood-2007-11-120998 [published Online First: 2008/03/21]