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Multiplex Immunohistochemical Analysis of the Spatial Immune Cell Landscape of the Tumor Microenvironment
Published on: August 18, 2023
Immunogenomic cancer evolution: A framework to understand cancer immunosuppression
Shogo Kumagai1,2,3, Yusaku Momoi1,4, Hiroyoshi Nishikawa1,5,6,7
1Division of Cancer Immunology, Research Institute, National Cancer Center, Tokyo 104-0045, Japan.
Science Immunology
|March 28, 2025
Summary
Cancer genetic changes drive immune evasion and resistance to immunotherapy by creating an immunosuppressive tumor microenvironment (TME). Understanding this immunogenomic evolution can guide precision medicine approaches combining immunotherapy with targeted therapies.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Tumor development involves immune evasion through mechanisms like reduced antigenicity and immunosuppressive molecule expression.
- Aberrant oncogenic signaling links cancer development with immune evasion.
- Genetic abnormalities in cancers, like EGFR mutations in lung cancer, promote an immunosuppressive tumor microenvironment (TME) beyond the cancer immunoediting hypothesis.
Purpose of the Study:
- To review current findings on the relationship between cancer genetic abnormalities and immunosuppression.
- To explore how these factors contribute to clinical resistance to immunotherapy.
- To propose new concepts for understanding cancer progression and treatment.
Main Methods:
- Review of recent scientific literature.
- Immunogenomic analysis of patient specimens.
- Integration of genomic and immunological data.
Main Results:
- Cancer genetic alterations actively shape an immunosuppressive TME.
- This immunosuppression leads to clinical resistance to immunotherapies.
- Oncogenic signaling plays a dual role in cancer initiation and immune evasion.
Conclusions:
- Introduce the concept of 'immunogenomic cancer evolution,' where genomic changes dictate the immunosuppressive TME.
- Propose 'immunogenomic precision medicine' for combining immunotherapy with targeted agents to overcome TME-mediated resistance.
- Highlight the need for integrated genomic and immunologic approaches in cancer therapy.
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