Understanding the immune response and the current landscape of immunotherapy in pancreatic cancer
- PMID: 34790007
- PMCID: PMC8567475
- DOI: 10.3748/wjg.v27.i40.6775
Understanding the immune response and the current landscape of immunotherapy in pancreatic cancer
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive tumor with high lethality. Even with surgery, radiotherapy, chemotherapy, and other locoregional or systemic therapies, the survival rates for PDAC are low and have not significantly changed in the past decades. The special characteristics of the PDAC's microenvironment and its complex immune escape mechanism need to be considered when designing novel therapeutic approaches in this disease. PDAC is characterized by chronic inflammation with a high rate of tumor-associated macrophages and myeloid-derived suppressor cells and a low rate of natural killer and effector T cells. The pancreatic microenvironment is a fibrotic, microvascularized stroma that isolates the tumor from systemic vascularization. Immunotherapy, a novel approach that has demonstrated effectiveness in certain solid tumors, has failed to show any practice-changing results in pancreatic cancer, with the exception of PDACs with mismatch repair deficiency and high tumor mutational burden, which show prolonged survival rates with immunotherapy. Currently, numerous clinical trials are attempting to assess the efficacy of immunotherapeutic strategies in PDAC, including immune checkpoint inhibitors, cancer vaccines, and adoptive cell transfer, alone or in combination with other immunotherapeutic agents, chemoradiotherapy, and other targeted therapies. A deep understanding of the immune response will help in the development of new therapeutic strategies leading to improved clinical outcomes for patients with PDAC.
Keywords: Cancer vaccines; Immune evasion; Immunity; Immunotherapy; Pancreatic cancer; Tumor microenvironment.
©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
Conflict of interest statement
Conflict-of-interest statement: Authors declare no conflict of interest for this manuscript.
Similar articles
-
Role of targeted immunotherapy for pancreatic ductal adenocarcinoma (PDAC) treatment: An overview.Int Immunopharmacol. 2021 Jun;95:107508. doi: 10.1016/j.intimp.2021.107508. Epub 2021 Mar 13. Int Immunopharmacol. 2021. PMID: 33725635 Review.
-
Current advances and outlooks in immunotherapy for pancreatic ductal adenocarcinoma.Mol Cancer. 2020 Feb 15;19(1):32. doi: 10.1186/s12943-020-01151-3. Mol Cancer. 2020. PMID: 32061257 Free PMC article. Review.
-
Anti-pancreatic tumor efficacy of a Listeria-based, Annexin A2-targeting immunotherapy in combination with anti-PD-1 antibodies.J Immunother Cancer. 2019 May 22;7(1):132. doi: 10.1186/s40425-019-0601-5. J Immunother Cancer. 2019. PMID: 31113479 Free PMC article.
-
Immunotherapy for pancreatic cancer: A 2020 update.Cancer Treat Rev. 2020 Jun;86:102016. doi: 10.1016/j.ctrv.2020.102016. Epub 2020 Mar 25. Cancer Treat Rev. 2020. PMID: 32247999 Review.
-
DPP inhibition alters the CXCR3 axis and enhances NK and CD8+ T cell infiltration to improve anti-PD1 efficacy in murine models of pancreatic ductal adenocarcinoma.J Immunother Cancer. 2021 Nov;9(11):e002837. doi: 10.1136/jitc-2021-002837. J Immunother Cancer. 2021. PMID: 34737215 Free PMC article.
Cited by
-
Time trend of pancreatic cancer mortality in the Western Pacific Region: age-period-cohort analysis from 1990 to 2019 and forecasting for 2044.BMC Cancer. 2023 Sep 18;23(1):876. doi: 10.1186/s12885-023-11369-1. BMC Cancer. 2023. PMID: 37723486 Free PMC article.
-
Development of a customizable mouse backbone spectral flow cytometry panel to delineate immune cell populations in normal and tumor tissues.Front Immunol. 2024 Mar 27;15:1374943. doi: 10.3389/fimmu.2024.1374943. eCollection 2024. Front Immunol. 2024. PMID: 38605953 Free PMC article.
-
Quantitative Spatial Profiling of Immune Populations in Pancreatic Ductal Adenocarcinoma Reveals Tumor Microenvironment Heterogeneity and Prognostic Biomarkers.Cancer Res. 2022 Dec 2;82(23):4359-4372. doi: 10.1158/0008-5472.CAN-22-1190. Cancer Res. 2022. PMID: 36112643 Free PMC article.
-
Burden of Gastrointestinal Tumors in Asian Countries, 1990-2021: An Analysis for the Global Burden of Disease Study 2021.Clin Epidemiol. 2024 Sep 4;16:587-601. doi: 10.2147/CLEP.S472553. eCollection 2024. Clin Epidemiol. 2024. PMID: 39252850 Free PMC article.
-
Suppression of the antitumoral activity of natural killer cells under indirect coculture with cancer-associated fibroblasts in a pancreatic TIME-on-chip model.Cancer Cell Int. 2023 Sep 27;23(1):219. doi: 10.1186/s12935-023-03064-9. Cancer Cell Int. 2023. PMID: 37759302 Free PMC article.
References
-
- 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, Tabernero J, Hidalgo M, Goldstein D, Van Cutsem E, Wei X, Iglesias J, Renschler MF. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med . 2013;369:1691–1703. - PMC - PubMed
-
- Seufferlein T, Bachet JB, Van Cutsem E, Rougier P ESMO Guidelines Working Group. Pancreatic adenocarcinoma: ESMO-ESDO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol . 2012;23 Suppl 7:vii33–vii40. - PubMed
Publication types
MeSH terms
LinkOut - more resources
Full Text Sources
Medical
Miscellaneous