916 Making their own off switch: Fgl2 produced by antigen-specific CD8+ T cells tempers the CD8+ T-cell response via apoptosis of FcγRIIB+ CD8+ T cells

BackgroundEffector CD8+ T-cell tumor infiltration is a critical factor to immunotherapeutic success. Our lab recently discovered that FcγRIIB, the sole inhibitory IgG-Fc receptor, is upregulated on effector-like memory CD8+ T cells at the tumor in mice and humans1–3 and signaling through FcγRIIB regulates CD8+ T cells in a cell-intrinsic manner. We discovered that fibrinogen-like protein 2 (Fgl2) binds FcγRIIB and induces FcγRIIB-mediated cell death, but the source of Fgl2 was unknown. Here, we investigate the possibility that CD8+ T cells produce Fgl2 in an auto-regulatory feedback loop.Methods In vivo mouse studies utilized the B16-OVA and B16-F10 melanoma mouse models. For melanoma patient tumor-infiltrating lymphocyte (TIL) studies, melanoma tumor tissues were collected (IRB #00095411), deidentified, and distributed by the Cancer Tissue and Pathology shared resource of Winship Cancer Institute of Emory University. Publicly available single-cell RNA-sequencing human data was analyzed using the BBrowser2 platform.4 5 ResultsHere, we show that CD8+ T cells can express and produce Fgl2 upon activation in mice and humans compared to unstimulated controls (p