CD93 Correlates With Immune Infiltration and Impacts Patient Immunotherapy Efficacy: A Pan-Cancer Analysis

Abstract

Background: The clinical implementation of immune-checkpoint inhibitors (ICIs) targeting CTLA4, PD-1, and PD-L1 has revolutionized the treatment of cancer. However, the majority of patients do not derive clinical benefit. Further development is needed to optimize the approach of ICI therapy. Immunotherapy combined with other forms of treatment is a rising strategy for boosting antitumor responses. CD93 was found to sensitize tumors to immune-checkpoint blocker therapy after the blockade of its pathway. However, its role in immune and ICB therapy across pan-cancer has remained unexplored.Methods: In this study, we provide a comprehensive investigation of CD93 expression in a pan-cancer manner involving 33 cancer types. We evaluated the association of CD93 expression with prognosis, mismatch repair, tumor mutation burden, and microsatellite instability, immune checkpoints, tumor microenvironment, and immune using multiple online datasets, including The Cancer Genome Atlas, Cancer Cell Line Encyclopedia, Genotype Tissue-Expression, cBioPortal, Tumor Immune Estimation Resource database, and Tumor Immune Single-cell Hub.Results: CD93 expression varied strongly among cancer types, and increased CD93 gene expression was associated with poor prognosis as well as higher immune factors in most cancer types. Additionally, the level of CD93 was significantly correlated with MMR, TMB, MSI, immune checkpoints, TME, and immune cell infiltration. Noticeably, our results mediated a strong positive contact between CD93 and CAFs, endothelial cells, myeloid dendritic cells, hematopoietic stem cells, mononuclear/macrophage subsets, and neutrophils while a negative correlation with Th1, MDSC, NK, and T-cell follicular helper in almost all cancers. Function analysis on CD93 revealed a link between itself and promoting cancers, inflammation, and angiogenesis.Conclusion: CD93 can function as a prognostic marker in various malignant tumors and is integral in TME and immune infiltration. Inhibition of the CD93 pathway may be a novel and promising strategy for immunotherapy in human cancer. Further explorations of the mechanisms of CD93 in the immune system may help improve cancer therapy methods.

The CXCL16-CXCR6 axis in glioblastoma modulates T-cell activity in a spatiotemporal context

“…Furthermore, differential expression analysis revealed increased proportions and degrees of expression of immunosuppression-related genes, such as RGS1, in CXCR6-positive T cells ( Figure 1B , left panel ). Examination of CXCL16-positive myeloid cells revealed enrichment of well-known immunosuppressive markers/phenotypes (C5Ar1 and CXCR4) ( 28 – 31 ) as well as inflammatory myeloid cells (CD93 and HLA-DPB1) ( 32 – 35 ), suggesting increased pleiotropic RNA expression in these subsets of GBM cells ( Figure 1B , right panel ).…”

Prophylactic treatment with Bacteroides uniformis and Bifidobacterium bifidum counteracts hepatic NK cell immune tolerance in nonalcoholic steatohepatitis induced by high fat diet

“… 34 Both anti- CD44 antibody and CD44 deficiency in mice mitigated liver steatosis, attenuated adipose inflammation, and improved glucose tolerance in diet-induced obese mice. 35 , 36 CD93 is also involved in NK cell immune tolerance and is negatively correlated with NK cells, 37 and anti- CD93 antibodies can increase the infiltration of NK cells. 38 In our study, B. uniformis transplantation statistically reduced the expression of hepatic CD44 and CD93 , offering another considerable mechanism by which it enhances NK cell infiltration and activation.…”

Reduced 2,4‐dienoyl‐CoA reductase 1 is served as an unfavorable biomarker and is related to immune infiltration in cervical cancer

“…6 Zhang et al found that CD93 is a biomarker for a variety of malignancies and is associated with immune infiltration, and that inhibition of the CD93 pathway affected the outcome of immunotherapy. 7 Surfactant protein A1 (SFTPA1) is a member of the C-type lectin subfamily. Lu et al performed immunofiltration analysis and revealed that it is quite important in the innate immune response.…”

“…Immune infiltration was the focus of immunotherapy 6 . Zhang et al found that CD93 is a biomarker for a variety of malignancies and is associated with immune infiltration, and that inhibition of the CD93 pathway affected the outcome of immunotherapy 7 . Surfactant protein A1 (SFTPA1) is a member of the C‐type lectin subfamily.…”