| First Author | Farley CR | Year | 2021 |
| Journal | JCI Insight | Volume | 6 |
| Issue | 4 | PubMed ID | 33616086 |
| Mgi Jnum | J:322264 | Mgi Id | MGI:6753653 |
| Doi | 10.1172/jci.insight.135623 | Citation | Farley CR, et al. (2021) FcgammaRIIB is a T cell checkpoint in antitumor immunity. JCI Insight 6(4) |
| abstractText | 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 FcgammaRIIB, 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 FcgammaRIIB-sufficient hosts resulted in an increased frequency of tumor-infiltrating CD8+ T cells with greater effector function. Finally, FcgammaRIIB was expressed on CD8+ memory T cells isolated from patients with melanoma. These data illuminate a cell-intrinsic role for the FcgammaRIIB checkpoint in suppressing tumor-infiltrating CD8+ T cells. |
