Immune checkpoints in B-cell Lymphoma: Still an Unmet challenge from Basic research to clinical practice

In the last decade, advancements in immunotherapy knowledge have highlighted CTLA-4, PD-1, LAG-3, TIM-3, and TIGIT, decisive immune checkpoints exhibiting within the tumor microenvironment (TME), as fundamental objects for cancer immunotherapy. The widespread clinical use of immune checkpoint inhibitors (ICls), employing PD-1/PD-L1 or CTLA-4 antibodies to obstruct crucial checkpoint regulators, is noted in treating B-cell lymphoma patients. Nevertheless, the prolonged advantages of the currently employed treatments against CTLA-4, PD-1, and PD-L1 are uncommon among patients. Thus, recent focus has been progressively moved to additional immune checkpoints on T cells, like LAG-3, TIM-3, and TIGIT, which are now seen as reassuring targets for treatment and broadly acknowledged. There are several types of immunecheckpoint molecules expressed by T cells, and inhibitors targeting immune checkpoints can revive and amplify the immune response of T lymphocytes against tumors, a crucial aspect in lymphoma therapy. However, there is little knowledge about their regulation. Herein, we discuss the anti-tumor effects and functions of ICIs in controlling T-cell activity, as well as the progress in combined application with other immunotherapies.