Immune Checkpoint and Inflammation As Therapeutic Targets in Pancreatic Carcinoma

Overview

Journal World J Gastroenterol

Publisher Baishideng Publishing Group

Specialty Gastroenterology

Date 2016 Sep 28

PMID 27672267

Citations 11

Authors

Shiro Kimbara

Shunsuke Kondo

Affiliations

Soon will be listed here.

Abstract

Pancreatic adenocarcinoma (PAC) is one of the most deadly malignant neoplasms, and the efficacy of conventional cytotoxic chemotherapy is far from satisfactory. Recent research studies have revealed that immunosuppression and inflammation are associated with oncogenesis, as well as tumor development, invasion, and metastasis in PAC. Thus, immunosuppression-related signaling, especially that involving immune checkpoint and inflammation, has emerged as novel treatment targets for PAC. However, PAC is an immune-resistant tumor, and it is still unclear whether immune checkpoint or anti-inflammation therapies would be an ideal strategy. In this article, we will review immune checkpoint and inflammation as potential targets, as well as clinical trials and the prospects for immunotherapy in PAC.

Citing Articles

Insights on the Role of Sialic Acids in Acute Lymphoblastic Leukemia in Children.

Radu K, Baek K Int J Mol Sci. 2025; 26(5).

PMID: 40076855 PMC: 11900591. DOI: 10.3390/ijms26052233.

Precision Targeting Strategies in Pancreatic Cancer: The Role of Tumor Microenvironment.

Vitorakis N, Gargalionis A, Papavassiliou K, Adamopoulos C, Papavassiliou A Cancers (Basel). 2024; 16(16).

PMID: 39199647 PMC: 11352254. DOI: 10.3390/cancers16162876.

The immunoregulation effect of tumor microenvironment in pancreatic ductal adenocarcinoma.

Zhang J, Li R, Huang S Front Oncol. 2022; 12:951019.

PMID: 35965504 PMC: 9365986. DOI: 10.3389/fonc.2022.951019.

Association of Tim-3/Gal-9 Axis with NLRC4 Inflammasome in Glioma Malignancy: Tim-3/Gal-9 Induce the NLRC4 Inflammasome.

Sim J, Park J, Kim S, Hwang S, Sung K, Lee J Int J Mol Sci. 2022; 23(4).

PMID: 35216164 PMC: 8878774. DOI: 10.3390/ijms23042028.

DBDx-based drug combinations show highly potent therapeutic efficacy against human pancreatic cancer xenografts in athymic mice.

Zheng Y, Zhang M, Li Y, Liu X, Zhen Y Cancer Biol Ther. 2020; 21(8):749-757.

PMID: 32644888 PMC: 7515518. DOI: 10.1080/15384047.2020.1776580.

References

Motzer R, Escudier B, Mcdermott D, George S, Hammers H, Srinivas S . Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015; 373(19):1803-13. PMC: 5719487. DOI: 10.1056/NEJMoa1510665. View

Le D, Uram J, Wang H, Bartlett B, Kemberling H, Eyring A . PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med. 2015; 372(26):2509-20. PMC: 4481136. DOI: 10.1056/NEJMoa1500596. View

Steele C, Karim S, Leach J, Bailey P, Upstill-Goddard R, Rishi L . CXCR2 Inhibition Profoundly Suppresses Metastases and Augments Immunotherapy in Pancreatic Ductal Adenocarcinoma. Cancer Cell. 2016; 29(6):832-845. PMC: 4912354. DOI: 10.1016/j.ccell.2016.04.014. View

Le D, Lutz E, Uram J, Sugar E, Onners B, Solt S . 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(7):382-9. PMC: 3779664. DOI: 10.1097/CJI.0b013e31829fb7a2. View

Suntharalingam G, Perry M, Ward S, Brett S, Castello-Cortes A, Brunner M . Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N Engl J Med. 2006; 355(10):1018-28. DOI: 10.1056/NEJMoa063842. View

Smolen J, Beaulieu A, Rubbert-Roth A, Ramos-Remus C, Rovensky J, Alecock E . Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet. 2008; 371(9617):987-97. DOI: 10.1016/S0140-6736(08)60453-5. View

Ferlay J, Parkin D, Steliarova-Foucher E . Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer. 2010; 46(4):765-81. DOI: 10.1016/j.ejca.2009.12.014. View

Brahmer J, Tykodi S, Chow L, Hwu W, Topalian S, Hwu P . Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012; 366(26):2455-65. PMC: 3563263. DOI: 10.1056/NEJMoa1200694. View

Ando K, Takahashi F, Motojima S, Nakashima K, Kaneko N, Hoshi K . Possible role for tocilizumab, an anti-interleukin-6 receptor antibody, in treating cancer cachexia. J Clin Oncol. 2012; 31(6):e69-72. DOI: 10.1200/JCO.2012.44.2020. View

10.

Martignoni M, Kunze P, Hildebrandt W, Kunzli B, Berberat P, Giese T . Role of mononuclear cells and inflammatory cytokines in pancreatic cancer-related cachexia. Clin Cancer Res. 2005; 11(16):5802-8. DOI: 10.1158/1078-0432.CCR-05-0185. View

11.

Lynch T, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R . Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. J Clin Oncol. 2012; 30(17):2046-54. DOI: 10.1200/JCO.2011.38.4032. View

12.

Alvarez R, Musteanu M, Garcia-Garcia E, Lopez-Casas P, Megias D, Guerra C . Stromal disrupting effects of nab-paclitaxel in pancreatic cancer. Br J Cancer. 2013; 109(4):926-33. PMC: 3749580. DOI: 10.1038/bjc.2013.415. View

13.

Feig C, Jones J, Kraman M, Wells R, Deonarine A, Chan D . 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. PMC: 3864274. DOI: 10.1073/pnas.1320318110. View

14.

Hodi F, ODay S, Mcdermott D, Weber R, Sosman J, Haanen J . Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010; 363(8):711-23. PMC: 3549297. DOI: 10.1056/NEJMoa1003466. View

15.

Bronte V, Zanovello P . Regulation of immune responses by L-arginine metabolism. Nat Rev Immunol. 2005; 5(8):641-54. DOI: 10.1038/nri1668. View

16.

Mantovani A, Bottazzi B, Colotta F, Sozzani S, Ruco L . The origin and function of tumor-associated macrophages. Immunol Today. 1992; 13(7):265-70. DOI: 10.1016/0167-5699(92)90008-U. View

17.

Gilmore T . Introduction to NF-kappaB: players, pathways, perspectives. Oncogene. 2006; 25(51):6680-4. DOI: 10.1038/sj.onc.1209954. View

18.

Bayliss T, Smith J, Schuster M, Dragnev K, Rigas J . A humanized anti-IL-6 antibody (ALD518) in non-small cell lung cancer. Expert Opin Biol Ther. 2011; 11(12):1663-8. DOI: 10.1517/14712598.2011.627850. View

19.

Zhao X, Li D, Zhu X, Gan W, Li Z, Xiong F . B7-H3 overexpression in pancreatic cancer promotes tumor progression. Int J Mol Med. 2012; 31(2):283-91. PMC: 4042878. DOI: 10.3892/ijmm.2012.1212. View

20.

McMillan D, Elahi M, Sattar N, Angerson W, Johnstone J, McArdle C . Measurement of the systemic inflammatory response predicts cancer-specific and non-cancer survival in patients with cancer. Nutr Cancer. 2002; 41(1-2):64-9. DOI: 10.1080/01635581.2001.9680613. View