New checkpoints in cancer immunotherapy

Abstract

Summary Immune responses must be fine‐tuned to allow effective clearance of invading pathogens, while maintain tolerance to self‐antigens. T cells are the major effector cells for fighting and killing tumor cells. Immune checkpoints play a pivotal role in T cell activation, and determine the functional outcome of T cell receptor (TCR) signaling. The blockade of immune checkpoints CTLA‐4 and PD‐1 has already been one of the most successful cancer immunotherapies. In this review, we will focus on three novel inhibitory B7 family checkpoint molecules, B7‐H3, B7S1 and VISTA. The aim of this article is to summarize their expressions in tumors as well as their roles in controlling and suppressing T cell immune responses and anti‐tumor immunity. These pathways may be explored in future cancer immunotherapy.

Expression and Significance of Immune Checkpoints in Clear Cell Carcinoma of the Uterine Cervix

“…The B7 family of immune checkpoints (PD-L1, PD-L2, B7-H3, B7-H4, and VISTA) suppress T cell function and play important roles in tumour immune evasion [21]. The blockade of immune checkpoints has achieved remarkable clinical success in treating human malignancies, and immunotherapy targeting novel checkpoints such as VISTA has attracted growing interest.…”

Introduction to checkpoint inhibitors and cancer immunotherapy

“…coblockade of the inhibitory receptors PD-1 and CTLA-4, 13 or PD-1 and Tim-3, 25 23 or PD-1 and TIGIT, 19 or PD-1 and Vista 20,22 can lead to better tumor clearance than blockade of each alone. It is not yet clear whether synergy results from coblockade on the same cell or different cells.…”

“…First, further work is needed to understand the extent to which inhibitory checkpoints provide redundant or unique functions, and whether there is a hierarchy in the orchestration of their signals. For example, coinhibitory receptors can be coexpressed on T cells, and coblockade of the inhibitory receptors PD‐1 and CTLA‐4, or PD‐1 and Tim‐3, or PD‐1 and TIGIT, or PD‐1 and Vista can lead to better tumor clearance than blockade of each alone. It is not yet clear whether synergy results from coblockade on the same cell or different cells.…”

Informatics for Cancer Immunotherapy

“…The relatively recent success of checkpoint blockade therapies in melanoma [332] , followed by other malignancies [333][334][335][336] , has motivated a resurgence of research into immune checkpoint receptors and their ligands [337,338] . The FDA has approved antibodies targeting CTLA-4 and PD-1/PD-L1, and new immune checkpoint targets are the subject of active investigation [339][340][341][342][343] .…”