Immunomodulation in Pancreatic Cancer

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2020 Nov 17

PMID 33198059

Citations 10

Authors

Mithunah Krishnamoorthy

John G Lenehan

Jeremy P Burton

Saman Maleki Vareki

Affiliations

Soon will be listed here.

Abstract

Pancreatic cancer has a high mortality rate, and its incidence is increasing worldwide. The almost universal poor prognosis of pancreatic cancer is partly due to symptoms presenting only at late stages and limited effective treatments. Recently, immune checkpoint blockade inhibitors have drastically improved patient survival in metastatic and advanced settings in certain cancers. Unfortunately, these therapies are ineffective in pancreatic cancer. However, tumor biopsies from long-term survivors of pancreatic cancer are more likely to be infiltrated by cytotoxic T-cells and certain species of bacteria that activate T-cells. These observations suggest that T-cell activation is essential for anti-tumor immunity in pancreatic cancers. This review discusses the immunological mechanisms responsible for effective anti-tumor immunity and how immune-based strategies can be exploited to develop new pancreatic cancer treatments.

Citing Articles

Innate and adaptive immune-directed tumour microenvironment in pancreatic ductal adenocarcinoma.

Mary Joseph A, Al Aiyan A, Al-Ramadi B, Singh S, Kishore U Front Immunol. 2024; 15:1323198.

PMID: 38384463 PMC: 10879611. DOI: 10.3389/fimmu.2024.1323198.

The Microbiome in Pancreatic Cancer-Implications for Diagnosis and Precision Bacteriophage Therapy for This Low Survival Disease.

Kabwe M, Dashper S, Tucci J Front Cell Infect Microbiol. 2022; 12:871293.

PMID: 35663462 PMC: 9160434. DOI: 10.3389/fcimb.2022.871293.

The Trinity: Interplay among Cancer Cells, Fibroblasts, and Immune Cells in Pancreatic Cancer and Implication of CD8 T Cell-Orientated Therapy.

Hung Y, Chen L, Hung W Biomedicines. 2022; 10(4).

PMID: 35453676 PMC: 9026398. DOI: 10.3390/biomedicines10040926.

Major histocompatibility complex class I molecule expression by pancreatic cancer cells is regulated by activation and inhibition of the epidermal growth factor receptor.

Knoche S, Larson A, Brumfield G, Cate S, Hildebrand W, Solheim J Immunol Res. 2022; 70(3):371-391.

PMID: 35303241 PMC: 9203924. DOI: 10.1007/s12026-022-09262-3.

The Immune Landscape of Human Pancreatic Ductal Carcinoma: Key Players, Clinical Implications, and Challenges.

Muller M, Haghnejad V, Schaefer M, Gauchotte G, Caron B, Peyrin-Biroulet L Cancers (Basel). 2022; 14(4).

PMID: 35205742 PMC: 8870260. DOI: 10.3390/cancers14040995.

References

Beatty G, Eghbali S, Kim R . Deploying Immunotherapy in Pancreatic Cancer: Defining Mechanisms of Response and Resistance. Am Soc Clin Oncol Educ Book. 2017; 37:267-278. DOI: 10.1200/EDBK_175232. View

Zhang Y, Velez-Delgado A, Mathew E, Li D, Mendez F, Flannagan K . Myeloid cells are required for PD-1/PD-L1 checkpoint activation and the establishment of an immunosuppressive environment in pancreatic cancer. Gut. 2016; 66(1):124-136. PMC: 5256390. DOI: 10.1136/gutjnl-2016-312078. View

Siegel R, Miller K, Jemal A . Cancer statistics, 2019. CA Cancer J Clin. 2019; 69(1):7-34. DOI: 10.3322/caac.21551. View

Babu Lankadasari M, Mukhopadhyay P, Mohammed S, Harikumar K . TAMing pancreatic cancer: combat with a double edged sword. Mol Cancer. 2019; 18(1):48. PMC: 6441154. DOI: 10.1186/s12943-019-0966-6. View

Dominguez G, Condamine T, Mony S, Hashimoto A, Wang F, Liu Q . Selective Targeting of Myeloid-Derived Suppressor Cells in Cancer Patients Using DS-8273a, an Agonistic TRAIL-R2 Antibody. Clin Cancer Res. 2016; 23(12):2942-2950. PMC: 5468499. DOI: 10.1158/1078-0432.CCR-16-1784. View

Erkan M, Kurtoglu M, Kleeff J . The role of hypoxia in pancreatic cancer: a potential therapeutic target?. Expert Rev Gastroenterol Hepatol. 2015; 10(3):301-16. DOI: 10.1586/17474124.2016.1117386. View

Gopalakrishnan V, Spencer C, Nezi L, Reuben A, Andrews M, Karpinets T . Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2017; 359(6371):97-103. PMC: 5827966. DOI: 10.1126/science.aan4236. View

Tsuchikawa T, Hirano S, Tanaka E, Matsumoto J, Kato K, Nakamura T . Novel aspects of preoperative chemoradiation therapy improving anti-tumor immunity in pancreatic cancer. Cancer Sci. 2013; 104(5):531-5. PMC: 7657202. DOI: 10.1111/cas.12119. View

Pushalkar S, Hundeyin M, Daley D, Zambirinis C, Kurz E, Mishra A . The Pancreatic Cancer Microbiome Promotes Oncogenesis by Induction of Innate and Adaptive Immune Suppression. Cancer Discov. 2018; 8(4):403-416. PMC: 6225783. DOI: 10.1158/2159-8290.CD-17-1134. View

10.

Orhan A, Vogelsang R, Andersen M, Madsen M, Holmich E, Raskov H . The prognostic value of tumour-infiltrating lymphocytes in pancreatic cancer: a systematic review and meta-analysis. Eur J Cancer. 2020; 132:71-84. DOI: 10.1016/j.ejca.2020.03.013. View

11.

Riquelme E, Zhang Y, Zhang L, Montiel M, Zoltan M, Dong W . Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes. Cell. 2019; 178(4):795-806.e12. PMC: 7288240. DOI: 10.1016/j.cell.2019.07.008. View

12.

He J, Ahuja N, Makary M, Cameron J, Eckhauser F, Choti M . 2564 resected periampullary adenocarcinomas at a single institution: trends over three decades. HPB (Oxford). 2013; 16(1):83-90. PMC: 3892319. DOI: 10.1111/hpb.12078. View

13.

Ene-Obong A, Clear A, Watt J, Wang J, Fatah R, Riches J . 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. PMC: 3896919. DOI: 10.1053/j.gastro.2013.07.025. View

14.

Ozdemir B, Pentcheva-Hoang T, Carstens J, Zheng X, Wu C, Simpson T . Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival. Cancer Cell. 2014; 25(6):719-34. PMC: 4180632. DOI: 10.1016/j.ccr.2014.04.005. View

15.

Von Hoff D, Ramanathan R, Borad M, Laheru D, Smith L, Wood T . Gemcitabine plus nab-paclitaxel is an active regimen in patients with advanced pancreatic cancer: a phase I/II trial. J Clin Oncol. 2011; 29(34):4548-54. PMC: 3565012. DOI: 10.1200/JCO.2011.36.5742. View

16.

Oda S, Anderson K, Ravikumar P, Bonson P, Garcia N, Jenkins C . A Fas-4-1BB fusion protein converts a death to a pro-survival signal and enhances T cell therapy. J Exp Med. 2020; 217(12). PMC: 7953733. DOI: 10.1084/jem.20191166. View

17.

Zhu Y, Knolhoff B, Meyer M, Nywening T, West B, Luo J . CSF1/CSF1R blockade reprograms tumor-infiltrating macrophages and improves response to T-cell checkpoint immunotherapy in pancreatic cancer models. Cancer Res. 2014; 74(18):5057-69. PMC: 4182950. DOI: 10.1158/0008-5472.CAN-13-3723. View

18.

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

19.

Ugel S, De Sanctis F, Mandruzzato S, Bronte V . Tumor-induced myeloid deviation: when myeloid-derived suppressor cells meet tumor-associated macrophages. J Clin Invest. 2015; 125(9):3365-76. PMC: 4588310. DOI: 10.1172/JCI80006. View

20.

Tanoue T, Morita S, Plichta D, Skelly A, Suda W, Sugiura Y . A defined commensal consortium elicits CD8 T cells and anti-cancer immunity. Nature. 2019; 565(7741):600-605. DOI: 10.1038/s41586-019-0878-z. View