Extended Data Fig. 8: A model for an inhibitory role of SUSD2 in effector CD8+ T cell antitumor immunity by modulating IL-2R signaling.
From: SUSD2 suppresses CD8+ T cell antitumor immunity by targeting IL-2 receptor signaling
The present study has identified SUSD2 as a negative regulator of IL-2-mediated effector CD8+ T cell functions and antitumor immunity. Both SUSD2 and IL-2Rα chain (IL-2Rα) contain the sushi domain (SD). Genetic ablation of SUSD2 (Susd2−/−) leads to elevated IFN-γ, GzmB and TNF production in effector CD8+ T cells and improved tumor growth control in multiple syngeneic tumor models. Mechanistically, SD-dependent interaction between SUSD2 and IL-2Rα competitively inhibits IL-2-IL-2Rα binding, leading to an attenuated IL-2R signaling. Therefore, SUSD2 represents a promising therapeutic target of tumor immunotherapy. Green and red arrows indicate promoting and inhibiting effect, respectively.
