B7x in cancer immunity and immunotherapy

B7x (also called B7-H4) is a co-inhibitory molecule of B7 family that is highly expressed in non-inflamed or cold cancers, and its aberrant expression is contributed to cancer progression and poor outcomes. B7x preferentially expresses on antigen-presenting cells (APCs) and in tumor cells, and it acts as an alternative anti-inflammatory immune checkpoint for hampering peripheral immune responses. Augmented infiltration of immunosuppressive cells, reduced proliferation and effector function of CD4+ and CD8+ T cells, and increased generation of regulatory T cells (Tregs) are outcomes of increased B7x activity in cancer. Evaluation of B7x in sera can be exploited as an effective biomarker of response in cancer patients. B7x overexpression generally occurs in programmed death-ligand 1 (PD-L1)- cancers and is involved in tumor resistance to anti-programmed death-1 (PD-1), anti-PDL1 or anti-cytotoxic T lymphocyte associated antigen-4 (CTLA-4) therapy. Co-expression of B7x receptor with PD1 on CD8+ T cells has made the anti-B7x a fruitful approach for reinvigoration of the functionality of exhausted T cells and is served as a complementary regimen in patients who are irresponsive to the common immune checkpoint inhibitor (ICI) therapy. An advance in the field is the development of bispecific antibodies against B7x with other regulatory molecules within tumor microenvironment (TME).

Automated summary

B7x is a co-inhibitory molecule highly expressed in non-inflamed cancers, contributing to cancer progression and poor outcomes. It hampers peripheral immune responses and promotes immunosuppressive cells and regulatory T cells in cancer. Evaluation of B7x in sera is a potential biomarker for cancer patient response. B7x overexpression is involved in tumor resistance to immune checkpoint inhibitor therapy, but anti-B7x treatment can reinvigorate exhausted T cells and complement conventional ICI therapy. The development of bispecific antibodies against B7x and other regulatory molecules is an advance in the field.