αTIGIT-IL2 通过促进肿瘤浸润性调节性 T 细胞脆性在小鼠模型中实现肿瘤消退

Administration of IL-2 may promote the suppressive function and proliferation of T reg cells that cause immune tolerance in patients with cancer, which causes low-dose IL-2 to fail in achieving an optimal anti-tumor effect.

Here, we designed an immunocytokine by fusing IL-2 and an anti-TIGIT monoclonal antibody, named αTIGIT-IL2, that targets T reg cells and promotes their fragility in the tumor milieu. These fragile-like T reg cells show impaired suppressive function and high IFN-γ production, triggering an immune-reactive tumor microenvironment.

Such inflammation leads to the recruitment and functional reprogramming of intratumoral neutrophils, improving cross-talk between neutrophils and CD8 + T cells and enhancing the antitumor ability of CD8 + T cells. Combination therapy with αTIGIT-IL2 and PD-1 blocker could eliminate triple-negative breast cancer (TNBC) tumors resistant to immune checkpoint blockade (ICB) therapy.

These findings provide the basis for developing a new generation of immunocytokines that target T reg cells and promote their fragility in the tumor milieu, resulting in robust antitumor immunity.