TIGIT and PD-L1 co-blockade promotes dendritic cell-dependent production of non-exhausted CD8(+) T cells.

Fc-active anti-TIGIT plus anti-PD-L1 therapy promotes a sequential cDC-centered costimulatory cascade that yields non-exhausted CD226+ CD8+ T cells.

• Why it matters: Anti-TIGIT efficacy depends on Fc binding, but how FcγR-expressing myeloid cells shape CD8+ T cell differentiation in tumors was unclear.
• What they did: In tumor models, conventional dendritic cells were required; intratumoral myeloid profiling showed FcR+ cDC1-like activation with higher CD80/CD86 and PVR, and CD28 signaling was required for therapy-induced CD226 on T cells.
• The result: cDC-derived PVR supported CD226-mediated non-exhausted CD8+ T cell differentiation, while FcγR-driven type I interferon maintained/amplified the cDC1-like state and exogenous IFN-I rescued anti-tumor immunity with Fc-inert anti-TIGIT plus anti-PD-L1.

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