Formate supplementation enhances anti-tumor CD8+ T cell fitness and efficacy of PD-1 blockade

Metabolic support of the response to immune checkpoint blockage is unknown. We used scRNA-seq to determine the response of CD8+ cells to metabolic supplementation with the one carbon donor formate in combination with anti-PD-1 Overall design: Tumor infiltrating CD8+ cells were purified by FACS on day 12 post implantation from B16-OVA tumors after treatment with formate (starting day 9) and antibody (starting day 10). Four treatment groups, control drinking water with isotype control antibody (C.I.), formate drinking water with isotype control antibody (F.I.), control drinking water with anti-PD-1 antibody (C.P.), and formate drinking water with anti-PD-1 antibody (F.P.).

免疫检查点阻断应答的代谢支持机制尚不明确。我们采用单细胞RNA测序（single-cell RNA sequencing, scRNA-seq）技术，探究一碳供体甲酸盐联合抗PD-1抗体进行代谢补充时，CD8+ T细胞的应答情况。
实验设计：在B16-OVA肿瘤模型中，对经甲酸盐（自第9日起给药）与抗PD-1抗体（自第10日起给药）处理的小鼠，于肿瘤接种后第12日通过荧光激活细胞分选（fluorescence-activated cell sorting, FACS）纯化肿瘤浸润性CD8+ T细胞。设置四组处理方案：常规饮水+同型对照抗体组（C.I.）、甲酸盐饮水+同型对照抗体组（F.I.）、常规饮水+抗PD-1抗体组（C.P.）以及甲酸盐饮水+抗PD-1抗体组（F.P.）。