补体 C1q 结合蛋白调节 T 细胞线粒体适应性，从而影响其存活、增殖和抗肿瘤免疫功能

T cells survival, proliferation, and anti-tumor response are closely linked to their mitochondrial health. Complement C1q binding protein (C1QBP) promotes mitochondrial fitness through regulation of mitochondrial metabolism and morphology.

However, whether C1QBP regulates T cell survival, proliferation, and anti-tumor immune function remains unclear.

Our data demonstrated that C1QBP knockdown induced the accumulation of reactive oxygen species (ROS) and the loss of mitochondrial membrane potential to impair T cell mitochondrial fitness. At the same time, C1QBP insufficiency reduced the recruitment of the anti-apoptotic proteins, including Bcl-2 and Bcl-XL, and repressed caspase-3 activation and poly (ADP-ribose) polymerase cleavage, which consequently accelerated the T cell apoptotic process.

In contrast, C1QBP knockdown rendered T cells with relatively weaker proliferation due to the inhibition of AKT/mTOR signaling pathway. To investigate the exact role of C1QBP in anti-tumor response, C1QBP +/- and C1QBP +/+ mice were given a subcutaneous injection of murine MC38 cells.

We found that C1QBP deficiency attenuated T cell tumor infiltration and aggravated tumor-infiltrating T lymphocytes (TIL) exhaustion.

Moreover, we further clarified the potential function of C1QBP in chimeric antigen receptor (CAR) T cell immunotherapy.

Our data showed that C1QBP +/- CAR T cells exhibited relatively weaker anti-tumor response than the corresponding C1QBP +/+ CAR T cells. Given that C1QBP knockdown impairs T cells' anti-apoptotic capacity, proliferation as well as anti-tumor immune function, development of the strategy for potentiation of T cells' mitochondrial fitness through C1QBP could potentially optimize the efficacy of the related immunotherapy.