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Review
. 2022 Jul;41(31):3821-3829.
doi: 10.1038/s41388-022-02406-7. Epub 2022 Jul 11.

Co-dependencies in the tumor immune microenvironment

Peiwen Chen  1 , Prasenjit Dey  2
Affiliations
Review

Co-dependencies in the tumor immune microenvironment

Peiwen Chen et al. Oncogene. 2022 Jul.

Abstract

Activated oncogenes and disrupted tumor suppressor genes (TSGs) not only endow aspiring cancer cells with new biological capabilities but also influence the composition and function of host cells in the tumor microenvironment (TME). These non-cancer host cells can in turn provide cancer cells with growth support and protection from the anti-tumor immune response. In this ecosystem, geospatially heterogenous "subTME" adds to the complexity of the "global" TME which bestows tumors with increased tumorigenic ability and resistance to therapy. This review highlights how specific genetic alterations in cancer cells establish various symbiotic co-dependencies with surrounding host cells and details the cooperative role of the host cells in tumor biology. These essential interactions expand the repertoire of targets for the development of precision cancer treatments.

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Conflict of interest statement

DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST

P.D. has a patent pending on targeting IL-33 in cancer (U.S. Provisional Patent Application, Serial No. 63/238,531). P.C. has nothing to disclose.

Figures

Figure 1:
Figure 1:. Molecular circuitry underlying reciprocal interactions between cancer cells intrinsic genetic aberrations and its TME.
Tumor intrinsic genetics aberrations mediates the recruitment and activation of immunosuppressive immune cells. The genetic events increase or decrease expression and secretion of cytokines and chemokines that modulates the differential recruitment and/or inhibition of immune cells. Abbreviations. ILC2: Innate lymphoid cell 2, TH2: T helper cell 2, MDSC: Myeloid derived suppressor cell, GM-CSF: granulocyte-macrophage colony-stimulating factor, PD-1: Programmed cell death protein 1 (CD279), PD-L1: Programmed death-ligand 1 (CD274), LOX: lysyl oxidase, IRF2: interferon regulatory factor 2.
Figure 2:
Figure 2:. Targeting symbiotic co-dependencies to maximize the effect of immunotherapy.
The bidirectional crosstalk observed between cancer cells and the TME is manifested on several levels, that creates an opportunity to target these interactions for cancer therapy. Abbreviations. CRC: colorectal cancer, PDAC: pancreatic ductal adenocarcinoma, LAC: lung adenocarcinoma, PCa: prostate cancer, FMT: Fecal microbiota transplantation, TKI: tyrosine kinase inhibitor, TGF-β: Transforming growth factor beta.
See this image and copyright information in PMC

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