Cytotoxic CD4+ exTregs expressing KLRG1 retain immunosuppressive function in cancer

KLRG1+ FoxP3- cytotoxic CD4+ Tconv in murine tumors and human ccRCC show a conserved terminally activated phenotype and immunosuppressive function, linked to IL-10 and granzyme B.

• Why it matters: Cytotoxic CD4+ T cells in cancer are controversial, and the mechanisms behind how KLRG1+ CD4+ subsets relate to tumor progression and immune suppression are unclear.
• What they did: The team profiled KLRG1+ Tconv across multiple murine tumor models and human ccRCC specimens using transcriptional/proteomic analyses, ex vivo suppression assays, and in vivo Treg fate mapping.
• The result: In vivo, KLRG1-targeted antibody depletion slowed tumor growth and improved survival more than anti-KLRG1 blockade, with responses associating with reduced intratumoral KLRG1+ Tconv and Tregs.

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