To kill a cancer: Targeting the immune inhibitory checkpoint molecule, B7-H3

作者：Ranjana Kanchan, David Doss, Parvez Κhan, Mohd W. Nasser, Sidharth Mahapatra · 发表于：Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · 年份：2022 · DOI：10.1016/j.bbcan.2022.188783 · 被引用次数：40 · 研究领域：Cancer Immunotherapy and Biomarkers、Immunotherapy and Immune Responses、Immune Cell Function and Interaction

Targeting the anti-tumor immune response via the B7 family of immune-regulatory checkpoint proteins has revolutionized cancer treatment and resulted in punctuated responses in patients. B7-H3 has gained recent attention given its prominent deregulation and immunomodulatory role in a multitude of cancers. Numerous cancer studies have firmly established a strong link between deregulated B7-H3 expression and poorer outcomes. B7-H3 has been shown to augment cancer cell survival, proliferation, metastasis, and drug resistance by inducing an immune evasive phenotype through its effects on tumor-infiltrating immune cells, cancer cells, cancer-associated vasculature, and the stroma. Given the complex interplay between each of these components of the tumor microenvironment, a deeper understanding of B7-H3 signaling properties is inherently crucial to developing efficacious therapies that can target and inhibit these cancer-promoting interactions. This review delves into the various ways B7-H3 acts as an immunomodulator to facilitate immune evasion and promote tumor growth and spread. With post-transcriptional and post-translational modifications giving rise to different active isoforms coupled with recent discoveries of its putative receptors, B7-H3 can perform diverse functions. Here, we first discuss the dual co-stimulatory/co-inhibitory functions of B7-H3 in the context of normal physiology and cancer. We then discuss the crosstalk facilitated by B7-H3 between stromal components an...