Interferon-Induced Transmembrane Protein 3 Shapes an Inflamed Tumor Microenvironment and Identifies Immuno-Hot Tumors

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.

The B7H4-PDL1 classifier stratifies immuno-phenotype in cervical cancer

“…Based on molecular characteristics, B7H4-high tumors could be defined as “cold” tumors, PDL1-high tumors were “hot” tumors, and co-low tumors were somewhere in between. Generally, patients with “hot” tumors exhibited a better prognosis and higher therapeutic response [ 17 – 19 ]. However, this assumption was not supported by survival analysis.…”

“…“Cold” tumors are featured with immunosuppressive TME and resistance to either immunotherapy or chemotherapy, but “hot” tumors exhibit higher response rates to these therapies, which are characterized by T cell infiltration, increased interferon-γ (IFN-γ) signaling, activation of inhibitory checkpoints (CTLA4, PDL1, etc. ), genomic instability and the activation of major histocompatibility complex class I (MHC-I) [ 19 , 24 ]. Driving the formation of “hot” tumors is a gradual and complicated process.…”

“…Cai et al . reported that IFITM3 was upregulated in inflamed tumors and could be used as a feasible biomarker [ 19 ]. Hu et al .…”

Dishevelled-Associated Activator of Morphogenesis 2 (DAAM2) Predicts the Immuno-Hot Phenotype in Pancreatic Adenocarcinoma

“…Given that immune and tumor cells were both present in the tissues that were subjected to RNA-seq, we next explored the differences in various immunological characteristics between High-DAAM2 and Low-DAAM2 subtypes referring to previous research ( Cai et al, 2021 ).…”

Identification of a Tumor Immunological Phenotype-Related Gene Signature for Predicting Prognosis, Immunotherapy Efficacy, and Drug Candidates in Hepatocellular Carcinoma

“…Tumor immunological phenotype (TIP) is an emerging concept to evaluate the immunological heterogeneity depending on the relative infiltration of immune cells ( 23 ), and tumors are generally classified into two TIPs: “hot” (inflamed) and “cold” (non-inflamed) ( 23 ). Particular genes and pathways genetically regulate the immunological phenotypes have been identified to aid immunotherapy ( 24 – 27 ). Wang et al.…”