Resisting T cell attack: tumor-cell-intrinsic defense and reparation mechanisms

  cytotoxic T lymphocytes


immunological synapse



Cytotoxic T lymphocytes (CTLs) are antigen-specific killer cells equipped to identify and eliminate host cells that have been altered through infection or transformation. Both chimeric antigen-receptor (CAR) T cell therapies and immune checkpoint blockade (ICB) therapies are based on successful elimination of tumor cells by cytotoxic effectors. In this opinion article, we outline cell-intrinsic mechanisms by which tumor cells defend against CTLs, highlighting pathways that confer resistance and proposing opportunities for combination therapies. We discuss how exogenous killing entities [e.g., supramolecular attack particles (SMAPs)] offer a novel strategy to circumvent cellular resistance mechanisms. Our opinion article highlights the importance of identifying, quantifying, and targeting tumor defense mechanisms at the interface between tumor cells and CTLs as a critical consideration in the development of immunotherapy approaches.

Discover the published article

Trends Cancer. 2022 Dec 31;S2405-8033(22)00264-3.doi: 10.1016/j.trecan.2022.12.003. Online ahead of print.
Resisting T cell attack: tumor-cell-intrinsic defense and reparation mechanisms
Brienne McKenzie, Salvatore Valitutti

Centre de Recherches en Cancérologie de Toulouse

Toulouse Cancer Research Center (Oncopole)

Toulouse – FR

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