Fc gamma RIIB is a T cell checkpoint in antitumor immunity

In the setting of cancer, T cells upregulate coinhibitory molecules that attenuate TCR signaling and lead to the loss of proliferative capacity and effector function. Checkpoint inhibitors currently in clinical use have dramatically improved mortality from melanoma yet are not effective in all patients, suggesting that additional pathways may contribute to suppression of tumor-specific CD8(+) T cell responses in melanoma. Here, we show that Fc gamma RIIB, an inhibitory Fc receptor previously thought to be exclusively expressed on B cells and innate immune cells, is upregulated on tumor-infiltrating effector CD8(+) T cells in an experimental melanoma model and expressed on CD8(+) T cells in patients with melanoma. Genetic deficiency of Fcgr2b resulted in enhanced tumor-infiltrating CD8(+) T cell responses and significantly reduced tumor burden. Adoptive transfer experiments of Fcgr2b(-/-) tumor antigen-specific T cells into Fc gamma RIIB-sufficient hosts resulted in an increased frequency of tumor-infiltrating CD8(+) T cells with greater effector function. Finally, Fc gamma RIIB was expressed on CD8(+) memory T cells isolated from patients with melanoma. These data illuminate a cell-intrinsic role for the Fc gamma RIIB checkpoint in suppressing tumor-infiltrating CD8(+) T cells.

Automated summary

In the context of cancer, the inhibitory Fc receptor FcγRIIB is upregulated on CD8(+) T cells in melanoma patients, and genetic deficiency of Fcgr2b enhances anti-tumor responses and reduces tumor burden. These findings suggest a cell-intrinsic role for FcγRIIB in suppressing tumor-infiltrating CD8(+) T cells.