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Existing data indicate an association between vitamin D deficiency and increased severity of respiratory distress due to COVID-19 infection, especially in high-risk populations. To date, the effect of vitamin D on immunogenicity to SARS-CoV-2 vaccines has been investigated solely in young healthcare workers in a few studies, yielding conflicting findings, yet highlighting that the response to immunization is inversely related to age. Vitamin D status can potentially influence the antibody titers in people with a previous (or naïve) SARS-CoV-2 infection and vaccination, given its role in immune regulatory functions. From this standpoint, vitamin D supplementation can help reduce the risk of SARS-CoV-2 infection, COVID-19 severity/mortality and rebalance immunological function, particularly in subjects with vigorous T lymphocyte responses to COVID-19. However, more research is needed to establish a correlation between vitamin D status and the generation of protective serological responses to SARS-CoV-2 vaccination.

Immune checkpoints (ICs) have pivotal roles in regulating immune responses. The inhibitory ICs in the tumor microenvironment (TME) have been implicated in the immune evasion of tumoral cells. Therefore, identifying and targeting these inhibitory ICs might be critical for eliminating tumoral cells. V-domain immunoglobulin suppressor of T cell activation (VISTA) is a novel inhibitory IC that is expressed on myeloid cells, lymphoid cells, and tumoral cells; therefore, VISTA can substantially regulate innate and adaptive anti-tumoral immune responses. Besides, growing evidence indicates that VISTA blockade can enhance the sensitivity of tumoral cells to conventional IC-based immunotherapy, e.g., cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors. In this regard, the current study aimed to review the current evidence about the structure and expression pattern of VISTA, its role in TME, the clinicopathological significance of VISTA, and its prognostic values in various cancers. Besides, this review intended to collect the lessons from the recent pre-clinical and clinical studies and propose a strategy to overcome tumor immune-resistance states.