Search

Simple Summary: B7H4 emerges as a promising therapeutic target exhibiting negative costimulatory activity and whose expression is aberrant in a wide range of solid tumours. This molecule has obtained increased attention as the immune checkpoint is highly expressed in immune "cold" tumours in which the presence of PD-1 and PD-L1- is minimal, making these tumours unresponsive to most currently used immunotherapies. Deficient expression of B7H4 in normal tissue and its overexpression in malignant neoplasms makes B7H4 an attractive immunotherapy agent with potentially lower toxicity than anti-PD-1 and PD-L1 treatment. Numerous clinical trials have evaluated B7H4 targeting immunotherapy using various treatment modalities, including monoclonal antibodies, bispecific antibodies, antibody-drug conjugates, and CAR T cells. In this review, we aimed to update the current state of knowledge regarding B7H4's role in tumour promotion and immune evasion and summarise results from clinical trials assessing immunotherapies targeting B7H4 in solid tumours. Anti-cancer immunotherapies entirely changed the therapeutic approach to oncological patients. However, despite the undeniable success of anti-PD-1, PD-L1, and CTLA-4 antibody treatments, their effectiveness is limited either by certain types of malignancies or by the arising problem of cancer resistance. B7H4 (aliases B7x, B7H4, B7S1, VTCN1) is a member of a B7 immune checkpoint family with a distinct expression pattern from classical immune checkpoint pathways. The growing amount of research results seem to support the thesis that B7H4 might be a very potent therapeutic target. B7H4 was demonstrated to promote tumour progression in immune "cold" tumours by promoting migration, proliferation of tumour cells, and cancer stem cell persistence. B7H4 suppresses T cell effector functions, including inflammatory cytokine production, cytolytic activity, proliferation of T cells, and promoting the polarisation of naïve CD4 T cells into induced Tregs. This review aimed to summarise the available information about B7H4, focusing in particular on clinical implications, immunological mechanisms, potential strategies for malignancy treatment, and ongoing clinical trials. [ABSTRACT FROM AUTHOR]

V-set domain-containing T-cell activation inhibitor 1 (aliases VTCN1, B7H4) participates in tumour immune escape by delivering inhibitory signals to T cells. The purpose of this article was to assess the B7H4 prognostic value in solid cancers. Three databases were searched for relevant articles. The main endpoints were overall survival (OS), disease-specific survival (DSS), progression-free survival (PFS), recurrence-free survival (RFS), and disease-free survival (DFS). Appropriate hazard ratios (HRs) were pooled. The R studio software (version 4.0.3) was used for data analysis. Thirty-one studies met the inclusion criteria. High expression of B7H4 was associated with worse OS (HR = 1.52, 95% CI: 1.37–1.68) but not with DSS (HR = 1.14, 95% CI: 0.49–2.63), RFS (HR = 1.77, 95% CI: 0.75–4.18), DFS (HR = 1.29, 95% CI: 0.8–2.09), or PFS (HR = 1.71, 95% CI: 0.91–3.2) in patients with solid cancers. High expression of B7H4 is associated with a poorer prognosis in patients with solid cancers. B7H4 is a promising prognostic biomarker and immunotherapeutic target for various solid cancers because of its activity in cancer immunity and tumourigenesis. [ABSTRACT FROM AUTHOR]

HHLA2 is a checkpoint from the B7 family that can play a co-stimulatory or co-inhibitory role in cancer, depending on the binding receptor. The aim of this meta-analysis was to assess the relationship between HHLA2 levels and its impact on the prognosis of patients with solid cancers. The study used data from PubMed, Embase, Web of Science (WOS), Cochrane and SCOPUS databases. The R studio software was used for the data analysis. The study assessed overall survival (OS), disease-specific survival (DSS), progression-free survival (PFS), recurrence-free survival (RFS), and disease-free survival (DFS) by pooling appropriate hazard ratios (HR). Eighteen studies (2880 patients' data) were included. High expression of HHLA2 was associated with worse OS (HR = 1.58, 95% CI: 1.23–2.03), shorter RFS (HR = 1.95, 95% CI: 1.38–2.77) and worse DFS (HR = 1.45, 95% CI: 1.01–2.09) in patients with solid cancers. The current study suggests that high expression of HHLA2 is associated with poorer prognosis in patients with solid cancers. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer (CRC) is one of the most prevalent malignant neoplasms worldwide, responsible for over 900,000 deaths yearly. As the immunotherapies targeting the PD-1/PD-L1 axis in CRC are effective only in microsatellite unstable tumours, which are 15% of all CRC cases, new targets of immune evasion are still needed. B7H3 has been reported to mediate immune escape and promote tumour progression in numerous malignancies, but it has yet to be fully elucidated in CRC. The study investigates whether B7H3 expression is related to MSI/MSS status, tumour infiltrating lymphocytes and cytokine composition in CRC. We found that B7H3 expression is upregulated in CRC tumours and independent of MSI/MSS status. B7H3 correlated positively with cytokines supporting tumour growth and was associated with M2-macrophage polarization. Additionally, TCGA analysis showed that high B7H3 expression in CRC tumours is related to decreased survival in CRC patients. Our findings provide a novel insight into B7H3's role in CRC immunity. The study aimed to assess the expression of B7H3 concerning clinicopathological and histological parameters, including MSI/MSS status, CD-8 cells, tumour-infiltrating lymphocytes (TILs), budding, TNM scale and grading. Moreover, we analyzed the B7H3-related pathways using available online datasets and the immunological context of B7H3 expression, through the 48-cytokine screening panel of cancer tissues homogenates, immunogenic features and immune composition. The study included 158 patients diagnosed with CRC. To assess B7H3 levels, we performed an immunohistochemistry method (IHC) and enzyme-linked immunosorbent assay (ELISA). To elucidate the immune composition of colorectal cancer, we performed the Bio-Plex Pro Human 48-cytokine panel. To study biological characteristics of B7H3, we used online databases. Expression of B7H3 was upregulated in CRC tumour tissues in comparison to adjacent noncancerous margin tissues. The concentrations of B7H3 in tumours were positively associated with T parameter of patients and negatively with tumour-infiltrating lymphocytes score. Additionally, Principal Component Analysis showed that B7H3 expression in tumours correlated positively with cytokines associated with M2-macrophages and protumour growth factors. The expression of B7H3 in tumours was independent of MSI/MSS status. These findings will improve our understanding of B7H3 role in colorectal cancer immunity. Our study suggests that B7-H3 is a promising potential target for cancer therapy. Further studies must clarify the mechanisms of B7H3 overexpression and its therapeutic importance in colorectal cancer. [ABSTRACT FROM AUTHOR]

The main aim of this work was to collect and present the polymorphisms that have been identified and tested and that may potentially have an influence on the effect of analgesic therapies. Opioid drugs are one of the most commonly used painkillers in the treatment of postoperative, neoplastic and post-traumatic pain. Opioid receptors and their types: μ, δ, κ, purinergic and adrenergic receptors contribute to nociceptive stimulation and their modulation. The analgesic effect induced by opioids is dependent on many factors, such as age, sex, body mass and the occurrence of different polymorphic variants of genes encoding opioid, purinergic and adrenergic receptors. Many polymorphisms have been identified within the following genes: OPRM, OPRK, OPRD, ADRB1 and P2RX7, encoding the following receptors: μ, κ, δ, purinergic P2X and β1-adrenergic. The most common polymorphism is the single nucleotide polymorphism (SNP-single nucleotide polymorphism). The occurrence of some polymorphic forms may generate differences in expression and have an impact on the physicochemical properties of receptors, which results in different levels of analgesia in the population and the generation of side effects. The relation between the occurrence of polymorphic variants of the genes of receptors participating in nociceptive stimulation and the increased or reduced demand for opioids necessary to achieve analgesia has been confirmed. Mechanisms in which polymorphisms affect the modification of the anesthetic response to opioids in most cases remain unknown. Further research on opioid, purinergic and adrenergic receptors polymorphisms may improve the effectiveness of opioid therapies by regulating the dose to the patient's individual pain phenotype, and may reduce the risk of side effects resulting from using too high doses of the drug. [ABSTRACT FROM AUTHOR]