JAML 促进 CD8 和 γδ T 细胞抗肿瘤免疫，是肿瘤免疫治疗的新靶点

T cells are critical mediators of antitumor immunity and a major target for cancer immunotherapy. Antibody blockade of inhibitory receptors such as PD-1 can partially restore the activity of tumor-infiltrating lymphocytes (TILs).

However, the activation signals required to promote TIL responses are less well characterized.

Here we show that the antitumor activity of CD8 and TIL is supported by interactions between junctional adhesion molecule-like protein (JAML) on T cells and its ligand coxsackie and adenovirus receptor (CXADR) within tumor tissue. Loss of JAML through knockout in mice resulted in accelerated tumor growth that was associated with an impaired TIL response and increased CD8 TIL dysfunction.

In mouse tumor models, therapeutic treatment with an agonistic anti-JAML antibody inhibited tumor growth, improved TIL activation, decreased markers of CD8 TIL dysfunction, and significantly improved response to anti-PD-1 checkpoint blockade.

Thus, JAML represents a novel therapeutic target to enhance both CD8 and TIL immunity.