Immunogenomic cancer evolution: A framework to understand cancer immunosuppression
Cet article passe en revue les connaissances récentes concernant les liens entre la présence d'anomalies génétiques dans les cellules cancéreuses et l'immunosuppression responsable de la résistance aux immunothérapies
The process of tumor development involves tumor cells eluding detection and suppression of immune responses, which can cause decreased tumor cell antigenicity, expression of immunosuppressive molecules, and immunosuppressive cell recruitment to the tumor microenvironment (TME). Immunologically and genomically integrated analysis (immunogenomic analysis) of patient specimens has revealed that oncogenic aberrant signaling is involved in both carcinogenesis and immune evasion. In noninflamed cancers such as epidermal growth factor receptor (EGFR)–mutated lung cancers, genetic abnormalities in cancer cells contribute to the formation of an immunosuppressive TME by recruiting immunosuppressive cells, which cannot be fully explained by the cancer immunoediting hypothesis. This review summarizes the latest findings regarding the links between cancer genetic abnormalities and immunosuppression causing clinical resistance to immunotherapy. We propose the concepts of immunogenomic cancer evolution, in which cancer cell genomic evolution shapes the immunosuppressive TME, and immunogenomic precision medicine, in which cancer immunotherapy can be combined with molecularly targeted reagents that modulate the immunosuppressive TME. Understanding the impacts of genetic abnormalities on immune responses to tumors can inform immunogenomic-based precision medicine.
Science Immunology , résumé, 2025