T cells are an important part of the body's immune system, helping not only to clear invading pathogens, such as viruses, but also to kill cancer cells.
In recent years, cellular immunotherapy, represented by CAR-T, transforms the T cells of cancer patients in vitro to make them recognize antigens on the surface of tumor cells, and then infuse these cells back into the patient to recognize and kill cancer cells the therapeutic effect. Since 2017, the FDA has successively approved 6 CAR-T cell therapies for the treatment of blood cancers such as leukemia and lymphoma. The successful application of CAR-T therapy has rekindled hope for many desperate people waiting for bone marrow matching, and also marked the arrival of the era of cell therapy.
However, after receiving CAR-T treatment, about 30%-40% of patients achieved durable remission, which also means that the treatment has limited effect on more than half of patients. In addition, CAR-T is not effective for solid tumors, and there is currently no CAR-T therapy for solid tumors on the market. Immune checkpoint therapy represented by PD-1/PD-L1 inhibitors is considered to have completely changed the pattern of cancer treatment and has a good therapeutic effect on a variety of cancers. But not all patients respond, and as treatment progresses, resistance emerges. Therefore, improving the effectiveness of PD-1 inhibitors or expanding their application scope has received high attention in clinical research.
Inhibiting protein tyrosine phosphatase 1B (PTP1B) on T cells can mobilize the body's immune response to cancer and help suppress tumor growth, according to research published in Cancer Discovery by researchers at Monash University in Australia. This study identified PTP1B as an intracellular immune checkpoint and a cancer therapeutic target. PTP1B is highly expressed in intratumoral T cells, and its deletion or inhibition can enhance the antitumor activity of T cells and increase the effectiveness of CAR-T cells against solid tumors. In this study, the research team found that high expression of PTP1B on T cells restricted T cell expansion and inhibited its cytotoxic effects, thereby promoting tumor growth.
The research team conducted validation experiments in mouse models and found that inhibiting PTP1B enhanced the response of cancer cells to PD-1 inhibitors. Specifically, T-cell-specific deletion or inhibition of PTP1B increased STAT5 signaling, which enhanced antigen-induced expansion and cytotoxicity of CD8+ T cells, resulting in tumor growth inhibition. In addition, inhibition of PTP1B also significantly enhanced the effectiveness of CAR-T cell therapy. More importantly, the deletion or inhibition of PTP1B can significantly enhance the ability of CAR-T cells to kill solid tumors (including breast cancer), which proposes a new approach for CAR-T cell therapy in the treatment of solid tumors.