Abstract
Interferon-induced transmembrane protein 3 (IFITM3) is an interferon-induced membrane protein, which has been identified as a functional gene in multiple human cancers. The role of IFITM3 in cancer has been preliminarily summarized, but its relationship to antitumor immunity is still unclear. A pancancer analysis was conducted to investigate the expression pattern and immunological role of IFITM3 based on transcriptomic data downloaded from The Cancer Genome Atlas (TCGA) database. Next, correlations between IFITM3 and immunological features in the bladder cancer (BLCA) tumor microenvironment (TME) were assessed. In addition, the role of IFITM3 in estimating the clinical characteristics and the response to various therapies in BLCA was also evaluated. These results were next confirmed in the IMvigor210 cohort and a recruited cohort. In addition, correlations between IFITM3 and emerging immunobiomarkers, such as microbiota and N6-methyladenosine (m6A) genes, were assessed. IFITM3 was enhanced in most tumor tissues in comparison with adjacent tissues. IFITM3 was positively correlated with immunomodulators, tumor-infiltrating immune cells (TIICs), cancer immunity cycles, and inhibitory immune checkpoints. In addition, IFITM3 was associated with an inflamed phenotype and several established molecular subtypes. IFITM3 expression also predicted a notably higher response to chemotherapy, anti-EGFR therapy, and immunotherapy but a low response to anti-ERBB2, anti-ERBB4, and antiangiogenic therapy. In addition, IFITM3 was correlated with immune-related microbiota and m6A genes. In addition to BLCA, IFITM3 is expected to be a marker of high immunogenicity in most human cancers. In conclusion, IFITM3 expression can be used to identify immuno-hot tumors in most cancers, and IFITM3 may be a promising pancancer biomarker to estimate the immunological features of tumors.
Highlights
Interferon-induced transmembrane protein 3 (IFITM3) is an interferon-induced membrane protein that contributes to conferring immunity to influenza A H1N1 virus, West Nile virus, and dengue virus [1]
A pancancer analysis of the expression and immunological characteristics of IFITM3 was first performed, and the results revealed that IFITM3 was highly correlated with immunological factors in most cancers, but the tightest correlation was found in bladder cancer (BLCA)
In the Oncomine database, we discovered that IFITM3 was highly expressed in several cancers but expressed at low levels in BLCA and prostate cancer
Summary
IFITM3 is an interferon-induced membrane protein that contributes to conferring immunity to influenza A H1N1 virus, West Nile virus, and dengue virus [1]. CD225 domain is one of most important domains in IFITM3 protein, which is a critical part of its antiviral properties by direct inhibition of membrane fusion [3, 4]. Emerging evidence suggests that IFITM3 regulates endocytic trafficking in the absence of infection as well. Spence et al reported that IFITM3 promotes the degradation of EGFR in lysosomes under EGF stimulation [5]. It is unclear whether this effect mediates the oncogenesis and progression of cancers
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
