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Co-dependencies in the tumor immune microenvironment

Oncogene volume 41, pages 3821–3829 (2022)Cite this article

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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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Fig. 1: Molecular circuitry underlying reciprocal interactions between cancer cells intrinsic genetic aberrations and its TME.
Fig. 2: Targeting symbiotic co-dependencies to maximize the effect of immunotherapy.

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Acknowledgements

This study was supported in part by 5R00CA218891-04 (PD); 1R01CA262822-01 (PD), The Roswell Park Alliance Foundation-62-2839-01 (PD); NCI Cancer Center Support Grant P30CA016056 (PD); NIH R00 CA240896 (PC), DoD Career Development Award W81XWH-21-1-0380 (PC), Cancer Research Foundation Young Investigator Award (PC), Lynn Sage Scholar Award (PC), American Cancer Society Institutional Research Grant IRG-21-144-27 (PC), philanthropic donation from Mindy Jacobson and the Bill Bass Foundation (PC). Figures created with BioRender.com.

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  1. Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA

    Peiwen Chen

  2. Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14263, USA

    Prasenjit Dey

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  1. Peiwen Chen
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  2. Prasenjit Dey
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PC and PD wrote, reviewed, and edited the manuscript. PD supervised the manuscript. PD generated the figures.

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Correspondence to Prasenjit Dey.

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

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Chen, P., Dey, P. Co-dependencies in the tumor immune microenvironment. Oncogene 41, 3821–3829 (2022). https://doi.org/10.1038/s41388-022-02406-7

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