Noncanonical CD11b on CD8+ T cells promotes cytotoxic effector function

Abstract

Cancer immunosurveillance largely relies on effector CD8+ T cells, yet surface determinants of cytotoxic competence within tumor-reactive populations remain incompletely defined. Using single-cell surface proteomics in a mouse breast cancer model, we identified a tumor-enriched subset of antigen-experienced CD8+ T cells expressing CD11b, a prototypic myeloid integrin. CD11b CD8 T cells were detected across mouse tumor models and human solid tumors and, within tumor-reactive populations, CD11b marked cells with greater cytotoxic potential. Following activation, naive CD8+ T cells induced ITGAM transcription and CD18-dependent CD11b surface expression. Mechanistically, CD11b localized to the peripheral adhesive ring of the immune synapse and promoted lytic-granule secretion. Accordingly, CD11b+ T cells exhibited enhanced TCR- and CAR-mediated tumor cell killing, whereas CD11b deletion impaired T cell antitumor activity. Together, these findings identify CD11b as an inducible, noncanonical component of the T cell immune synapse that marks cytotoxic competence and promotes antitumor T cell function.