IGSF11 and VISTA: a pair of promising immune checkpoints in tumor immunotherapy

Abstract

Immunotherapy has become the major treatment for tumors in clinical practice, but some intractable problems such as the low response rate and high rates of immune-related adverse events still hinder the progress of tumor immunotherapy. Hence, it is essential to explore additional immunotherapy treatment targets. In this review, we focus on the structure, expression and expression-related mechanisms, interactions, biological functions and the progress in preclinical/clinical research of IGSF11 and VISTA in tumors. We cover the progress in recent research with this pair of immune checkpoints in tumor immune regulation, proliferation, immune resistance and predictive prognosis. Both IGSF11 and VISTA are highly expressed in tumors and are modulated by various factors. They co-participate in the functional regulation of immune cells and the inhibition of cytokine production. Besides, in the downregulation of IGSF11 and VISTA, both inhibit the growth of some tumors. Preclinical and clinical trials all emphasize the predictive role of IGSF11 and VISTA in the prognosis of tumors, and that the predictive role of the same gene varies from tumor to tumor. At present, further research is proving the enormous potential of IGSF11 and VISTA in tumors, and especially the role of VISTA in tumor immune resistance. This may prove to be a breakthrough to solve the current clinical immune resistance, and most importantly, since research has focused on VISTA but less on IGSF11, IGSF11 may be the next candidate for tumor immunotherapy.

Co-expression of immune checkpoints in glioblastoma revealed by single-nucleus RNA sequencing and spatial transcriptomics

“…reported that increased expression of VSIG-3 in glioma tissue is associated with high infiltration of immune cells (especially CD4 + and CD8 + T cells), in addition, the expression of IL-10 and TGF-β increases with increased VISTA expression [42] . Xi Yang Tang et al have speculated that VISTA may interact with IGSF11 for immune regulation in other tumors, including non-small cell lung cancer, ovarian cancer, gastric cancer, colorectal cancer, soft tissue sarcoma, and oral squamous cell carcinoma [48] . The Vista-targeting antibody HMBD-002 can effectively block the interaction between VISTA and IGSF11, further inhibiting IGSF11-mediated T cell production of IFN-γ [49] .…”

H-VISTA Immunohistochemistry Score Is Associated with Advanced Stages in Cutaneous and Ocular Melanoma

“…For example, in breast cancer, VISTA expression was associated with a better prognosis in triple-negative patients [29,30]. In other types of tumors, such as gliomas, endometrial cancer, prostate cancer, and mesothelioma, the expression varies after treatment; however, in most of these cases, positivity and high expression are related to an advanced stage and poor outcome [31][32][33][34].…”

Different expression patterns of VISTA concurrent with PD-1, Tim-3, and TIGIT on T cell subsets in peripheral blood and bone marrow from patients with multiple myeloma

“…Similarly, VISTA offers another compensatory inhibitory pathway in prostate tumors after anti-CTLA-4 therapy ( 34 ). In summary, VISTA is considered a potential therapeutic target for anticancer therapy that plays a vital role in immunosuppression ( 35 ). However, little is known about VISTA expression and its relevant mechanisms in MM.…”