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Cancer Immune Evasion through Genetic Immune Escape

Francisco Martínez-Jiménez/LinkedIn

Dec 7, 2024, 19:32

Cancer Immune Evasion through Genetic Immune Escape

Marco Donia, Senior Consultant, Clinician-Scientist and Junior Research Group Leader at the University of Copenhagen Herlev Hospital, posted on LinkedIn about recent paper by Francisco Martínez-Jiménez and Diego Chowell titled “Genetic immune escape in cancer: timing and implications for treatment” published on Science Direct.

Authors: Francisco Martínez-Jiménez, Diego Chowell

“Cancer Immune Evasion through Genetic Immune Escape.

Key Insights on Genetic Immune Escape (GIE):
1. Tumor-Intrinsic Mechanism: GIE is a tumor-specific alteration enabling immune evasion, primarily through mechanisms like:
Loss of heterozygosity (LOH) of HLA-I, HLA-II or B2M alterations, disrupting antigen presentation.
Disruption of IFN-g pathway
Alteration of CD58
2. Early Tumor Evolution: GIE often emerges in the early stages of tumorigenesis
3. Prevalence Across Cancers: GIE alterations are common but vary widely across cancer types. High mutational burden cancers (e.g., non-small cell lung cancer) show elevated rates of GIE, while low-burden tumors may employ alternative immune evasion pathways.

Clinical Implications:
Therapies targeting GIE mechanisms could restore immune system functionality and improve immunotherapy efficacy.
Identifying GIE in early or premalignant lesions offers potential for personalized immunoprevention strategies.

Understanding GIE as a tumor-intrinsic mechanism is critical to advancing cancer treatment and developing targeted (immuno)therapies.”

Marco Donia is a Senior Consultant, Clinician-Scientist and Junior Research Group Leader (TIL group) at the Department of Oncology and Center for Cancer Immune Therapy, University of Copenhagen Herlev Hospital, Denmark. He serves as an Associate Professor in Clinical Oncology at the University of Copenhagen. Donia is also a clinical oncologist treating patients with cancer immunotherapy. His research group is currently investigating new immune-regulatory circuits in PD-1/PD-L1 resistant tumors.