Cancer immunotherapy is a rapidly developing field of medicine that aims to use the host\'s immune mechanisms to inhibit and eliminate cancer cells. Antibodies targeting CTLA-4, PD-1, and its ligand PD-L1 are used in various cancer therapies. However, the most thoroughly researched pathway targeting PD-1/PD-L1 has many limitations, and multiple malignancies resist its effects. Human endogenous retrovirus-H Long repeat-associating 2 (HHLA2, known as B7H5/B7H7/B7y) is the youngest known molecule from the B7 family. HHLA2/TMIGD2/KIRD3DL3 is one of the critical pathways in modulating the immune response. Recent studies have demonstrated that HHLA2 has a double effect in modulating the immune system. The connection of HHLA2 with TMIGD2 induces T cell growth and cytokine production via an AKT-dependent signaling cascade. On the other hand, the binding of HHLA2 and KIR3DL3 leads to the inhibition of T cells and mediates tumor resistance against NK cells. This review aimed to summarize novel information about HHLA2, focusing on immunological mechanisms and clinical features of the HHLA2/KIR3DL3/TMIGD2 pathway in the context of potential strategies for malignancy treatment.

UNASSIGNED: Oral squamous cell carcinoma (OSCC) is the most common cancerous lesion in the oral cavity. During recent years, no significant reduction in the survival rate has been observed.
UNASSIGNED: To systematically review the literature and to summarise correlations between B7 family proteins and prognosis in OSCC.
UNASSIGNED: A systematic review of the literature about B7-H1 (PD-L1) and B7-DC (PD-L2) was carried out, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Thirty-six articles published before 22 May 2020 were included in the systematic review.
UNASSIGNED: The biggest study group consisted of 305 patients and the smallest - 10 patients. PD-L1 proved to be a prognostic factor in patients with OSCC. Immunohistochemistry was the most commonly used diagnostic method.
UNASSIGNED: Any mutations in the gene encoding PD-L1 and quantitative or functional changes in the status of PD-L1 may be important in the prognosis of OSCC.

Melanoma is currently known as one of the most aggressive malignant tumors. The prognostic factors and particularities of this neoplasm are a persistent hot topic in the medical field. This review has multiple purposes. First, we aim to summarize the known data regarding the histological and immunohistochemical appearance of this versatile tumor and to look further into the analysis of several widely used prognostic markers, such as B-Raf proto-oncogene, serine/threonine kinase BRAF. The second purpose is to analyze the data on the new prognostic markers, V-domain Immunoglobulin Suppressor of T cell Activation (VISTA) and Programmed death-ligand 1 (PD-L1). VISTA is a novel target that is considered to be highly important in determining the invasive potential and treatment response of a melanoma, and there are currently only a limited number of studies describing its role. PD-L1 is a marker with whose importance has been revealed in multiple types of malignancies, but its exact role regarding melanoma remains under investigation. In conclusion, the gathered data highlights the importance of correlations between these markers toward providing patients with a better outcome.

The members of the B7 family, as immune checkpoint molecules, can substantially regulate immune responses. Since microRNAs (miRs) can regulate gene expression post-transcriptionally, we conducted a scoping review to summarize and discuss the regulatory cross-talk between miRs and new B7 family immune checkpoint molecules, i.e., B7-H3, B7-H4, B7-H5, butyrophilin like 2 (BTNL2), B7-H6, B7-H7, and immunoglobulin like domain containing receptor 2 (ILDR2). The current study was performed using a six-stage methodology structure and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. PubMed, Embase, Scopus, Cochrane, ProQuest, and Google Scholar were systematically searched to obtain the relevant records to 5 November 2020. Two authors independently reviewed the obtained records and extracted the desired data. After quantitative and qualitative analyses, we used bioinformatics approaches to extend our knowledge about the regulatory cross-talk between miRs and the abovementioned B7 family members. Twenty-seven articles were identified that fulfilled the inclusion criteria. Studies with different designs reported gene-miR regulatory axes in various cancer and non-cancer diseases. The regulatory cross-talk between the aforementioned B7 family molecules and miRs might provide valuable insights into the pathogenesis of various human diseases.

In the last few years, V-domain Ig-containing suppressor of T cell activation(VISTA) has been reported as a prognostic biomarker in articles including various solid tumours. However, their conclusions have been controversial. For this reason, we performed this meta-analysis to further verify the prognostic value of VISTA in solid tumours. All relevant literature was identified from PubMed, Embase, the Cochrane Library and Web of Science. Ten studies, including 2, 440 patients, were eligible for the analysis. The pooled results showed that high expression of VISTA was associated with favourable overall survival (OS) than that seen with low expression of VISTA (7 studies, hazard ratio (HR) = 0.75, 95% confidence interval (CI): 0.66-0.86, P < 0.001). In addition, high expression of VISTA significantly correlated with high numbers of CD8 (+) tumour infiltrating lymphocytes (TILs) (3 studies, risk ratio (RR) = 1.80, 95% CI: 1.41-2.31, P < 0.001). In conclusion, these results indicate that VISTA is a potential prognostic biomarker in solid tumours.

B7-H6 is a co-stimulatory molecule discoveried recently. B7-H6 is not expressed on normal cells, but specially expressed on tumor cells. It can also be expressed on antigen presenting cells (APC) by the induction. The B7-H6 expression can be downregulated by HDACi. NK cells can be activated to release TNFα and IFNγ through B7H6-NKp30 pathway. The B7-H6 molecules expressed on the cell surface can be shedded to form soluble molecules. In the meantime, the B7-H6/NKp30 pathway may be involved in the pathogenesis of primary Sjogren syndrome. B7-H6/NKp30 may become a new therapeutic target for tumor, inflammation and autoimmune diseases. This review discusses the B7-H6 and receptor sructure, the expression and significance of B7-H6, the function and regulating mechanism of B7-H6 and the soluble molecules of B7-H6.

A number of members of the B7 superfamily of ligands have been implicated in tumor immunogenicity and cancer development. Two of these recently characterized ligands, B7-H4 and B7-H3, have been linked to ovarian tumors. B7-H4 is consistently overexpressed in ovarian tumor specimens, and its tissue and serum levels have been found to be a potential biomarker for ovarian cancer, either alone or in combination with CA125. More recently, B7-H3 has been found to be overexpressed in a large series of ovarian cancer tumor specimens and similar to other types of carcinomas, B7-H3 overexpression has been correlated with poor survival. On the basis of the results obtained by knocking down B7-H3 protein using siRNA, researchers have suggested that blocking the action of B7-H3 could reduce tumor growth, metastatic potential, and improve survival. Because siRNA knock-down is not an ideal clinical therapeutic vehicle, additional studies using antibody-mediated suppression of the B7-H3 protein are necessary to fully evaluate the clinical potential of this molecule as a therapeutic target.