Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Feb 7:15:1323198.
doi: 10.3389/fimmu.2024.1323198. eCollection 2024.

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

Ann Mary Joseph  1 , Ahmad Al Aiyan  1 , Basel Al-Ramadi  2   3   4 , Shiv K Singh  5 , Uday Kishore  1   3
Affiliations
Review

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

Ann Mary Joseph et al. Front Immunol. .

Abstract

One of the most deadly and aggressive cancers in the world, pancreatic ductal adenocarcinoma (PDAC), typically manifests at an advanced stage. PDAC is becoming more common, and by the year 2030, it is expected to overtake lung cancer as the second greatest cause of cancer-related death. The poor prognosis can be attributed to a number of factors, including difficulties in early identification, a poor probability of curative radical resection, limited response to chemotherapy and radiotherapy, and its immunotherapy resistance. Furthermore, an extensive desmoplastic stroma that surrounds PDAC forms a mechanical barrier that prevents vascularization and promotes poor immune cell penetration. Phenotypic heterogeneity, drug resistance, and immunosuppressive tumor microenvironment are the main causes of PDAC aggressiveness. There is a complex and dynamic interaction between tumor cells in PDAC with stromal cells within the tumour immune microenvironment. The immune suppressive microenvironment that promotes PDAC aggressiveness is contributed by a range of cellular and humoral factors, which itself are modulated by the cancer. In this review, we describe the role of innate and adaptive immune cells, complex tumor microenvironment in PDAC, humoral factors, innate immune-mediated therapeutic advances, and recent clinical trials in PDAC.

Keywords: EMT; PDAC; TME; TNF-α; immune suppression; immune surveillance; macrophages.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
Schematic representation of the PDAC TME compared to normal pancreatic tissue. Fibroblast activated in the tissue to CAFs are the dominant cell type in PDAC along with M2 TAMs and MDSC. The dense desmoplastic reaction and collapsed blood vessels provide barriers to cytotoxic T cell infiltration. PDAC, pancreatic ductal adenocarcinoma; ECM, extracellular matrix; PSC, pancreatic stellate cell; CAF, cancer-associated fibroblast;Treg, regulatory T cell; Breg, regulatory B cell; TAM, tumour-associated macrophage; TAN, tumour-associated neutrophil.
Figure 2
Figure 2
Schematic and H&E sections PDAC (Scale: 200 μm) to distinguish between Classical and Basal like subtypes in PDAC (64), summarising the clinicopathological differences, genetic signatures and therapy responses.
Figure 3
Figure 3
PDAC’s dense desmoplastic stroma and tumour microenvironment are depicted schematically here. The PDAC stroma is largely made up of CAFs, Macrophages, MDSCs and other immune cells. Exosomes produced from PDAC cells recruits and activates CAFs. Cytokines, TGF-β, IL-1, PDGF, SHH are cruicial for CAF activation. N2 TANs, myCAF, Tregs and Bregs have protumourigenic role. iCAF-inflammatory CAF, myCAF-myofibroblastic CAF, apCAF-antigen presenting CAF.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Cascinu S, Falconi M, Valentini V, Jelic S. ESMO Guidelines Working Group. Pancreatic cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol (2010) 21(Suppl 5):v55–8. doi: 10.1093/annonc/mdq165 - DOI - PubMed
    1. Haeberle L, Esposito I. Pathology of pancreatic cancer. Transl Gastroenterol Hepatol (2019) 4:50. doi: 10.21037/tgh.2019.06.02 - DOI - PMC - PubMed
    1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistic. CA: A Cancer J Clin (2022) 72(1):7–33. doi: 10.3322/caac.21708 - DOI - PubMed
    1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. . Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin (2021) 71(3):209–49. doi: 10.3322/caac.21660 - DOI - PubMed
    1. Khalaf N, El-Serag HB, Abrams HR, Thrift AP. Burden of pancreatic cancer: from epidemiology to practice. Clin Gastroenterol Hepatol (2021) 19(5):876–84. doi: 10.1016/j.cgh.2020.02.054 - DOI - PMC - PubMed

Publication types

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. AJ, BA-R and UK are funded by UAEU (Grant Number- 12F043).