Antifungal immunity mediated by C-type lectin receptors may be a novel target in immunotherapy for urothelial bladder cancer

Abstract

Immunotherapies, such as immune-checkpoint blockade and adoptive T-cell therapy, offer novel treatment options with good efficacy for patients with urothelial bladder cancer. However, heterogeneity and therapeutic resistance have limited the use of immunotherapy. Further research into immune-regulatory mechanisms in bladder cancer is urgently required. Emerging evidence demonstrates that the commensal microbiota and its interactions with host immunity play pivotal roles in a variety of physiological and pathological processes, including in cancer. The gut microbiota has been identified as a potentially effective target of treatment that can be synergized with immunotherapy. The urothelial tract is also a key site for multiple microbes, although the immune-regulatory role of the urinary microbiome in the process of carcinogenesis of bladder cancer remains to be elucidated. We performed a comprehensive analysis of the expression and biological functions of C-type lectin receptors (CLRs), which have been recognized as innate pathogen-associated receptors for fungal microbiota, in bladder cancer. In line with previous research on fungal colonization of the urothelial tract, we found that CLRs, including Dectin-1, Dectin-2, Dectin-3, and macrophage-inducible Ca2+-dependent lectin receptor (Mincle), had a significant association with immune infiltration in bladder cancer. Multiple innate and adaptive pathways are positively correlated with the upregulation of CLRs. In addition, we found a significant correlation between the expression of CLRs and a range of immune-checkpoint proteins in bladder cancer. Based on previous studies and our findings, we hypothesize that the urinary mycobiome plays a key role in the pathogenesis of bladder cancer and call for more research on CLR-mediated anti-fungal immunity against bladder cancer as a novel target for immunotherapy in urothelial bladder cancer.

CLEC7A regulates M2 macrophages to suppress the immune microenvironment and implies poorer prognosis of glioma

“…The protein dectin-1, encoded by CLEC7A, emerges as a promising candidate for therapeutic intervention. Its potential therapeutic significance has been documented in urothelial bladder cancer and intestinal tumors ( 18 , 19 ). To investigate the relationship between CLEC7A and gliomas, we first performed expression and survival analysis based on data from different databases and clinical patient information.…”

Targeted therapies in bladder cancer: signaling pathways, applications, and challenges

“…Interestingly, new immunotherapeutic alternatives such as mRNA vaccines, cytokines, and antifungal immunotherapies are being developed. 240,241 Owing to features of the specific and targetable antigens, ADCs are particularly effective for treating patients undergoing chemotherapy with local or metastatic advanced UC. These revolutionary drugs have provided hope to patients with mUC.…”

“…Therefore, a combination of checkpoint therapies and other treatment agents may improve the treatment outcomes of most patients with BC. Interestingly, new immunotherapeutic alternatives such as mRNA vaccines, cytokines, and antifungal immunotherapies are being developed 240,241 …”