Expression of tumor necrosis factor receptor 2 in human non‐small cell lung cancer and its role as a potential prognostic biomarker

Abstract

Background Tumor necrosis factor receptor 2 (TNFR2) promotes tumor cell proliferation, activates immunosuppressive cells, and supports immune escape. However, its role in non‐small cell lung cancer (NSCLC) has not been reported. Methods Quantitative real‐time PCR and Western blotting were used to evaluate TNFR2 in three NSCLC cell lines (A549, H1299, H1975) and normal lung epithelial cells (BEAS‐2B). TNFR2 was evaluated in 71 tumor tissues and 25 adjacent normal lung tissues by immunohistochemistry and analyzed with respect to clinical parameters. Results The messenger RNA and protein levels of TNFR2 were significantly higher in A549, H1299, and H1975 cells than in BEAS‐2B cells ( P < 0.05) and differed significantly between NSCLC tissues and adjacent normal lung tissues by immunohistochemistry ( P < 0.0001). TNFR2 is a independent prognostic factor in NSCLC. There have significantly differences in overall survival (OS) ( P = 0.006) and disease‐free survival (DFS) ( P = 0.000) of NSCLC patients between TNFR2 low expression groups and TNFR2 high expression group. Conclusion TNFR2 is expressed in human NSCLC tissues and cell lines and is related to poor prognosis. TNFR2 may represent a new auxiliary index for patients with NSCLC.

Dual Role of TNF and LTα in Carcinogenesis as Implicated by Studies in Mice

“…Knocking down TNFR2 in Lewis lung carcinoma cells combined with a low dose of recombinant mouse TNF significantly inhibited carcinoma growth in WT mice, suggesting that TNF/TNFR2 signaling in tumor cells is pro-tumorigenic in this transplantable tumor model [ 22 ]. In line with this, TNFR2 expression by human non-small cell lung cancer tissue is related to a poor prognosis [ 38 ]. Chronic inflammation is an independent risk factor and a cancer hallmark [ 39 ].…”

TNFR2: Role in Cancer Immunology and Immunotherapy

“… 102 Another IHC study from 71 primary human non-small cell lung carcinoma (NSCLC) patients and 25 normal tissue samples found that tumor tissues express markedly higher TNFR2 than normal tissues, and the rate of TNFR2 hi expression in NSCLC tissue is 35%. 103 Moreover, human NSCLC cell lines (A549, H1299, and H1975) also express markedly higher TNFR2 in both mRNA and protein levels than those in the normal human lung epithelial cell line (BEAS-2B). 103 We analyzed TCGA (The Cancer Genome Atlas) and GTEx (Genotype-Tissue Expression) database with web-based tool Gene Expression Profiling Interactive Analysis (GEPIA, http://gepia2.cancer-pku.cn/ ), and found that the overall abundance of TNFR2 gene expression is markedly higher than that of PD-L1 and CTLA-4 in the most of tumor tissues ( Figure 1 ).…”

Recruitment and Expansion of Tregs Cells in the Tumor Environment—How to Target Them?

“…In tumor context, the scRNA-seq analysis of TILs highlighted the upregulation of TNFR2 on TA-Tregs compared to other TA-T cell subsets, except for some TA-CD8 + T RM [ 45 , 49 ]. At the protein level, TNFR2 is upregulated in the TME compared to patient blood in different cancers, such as in NSCLC [ 180 ], cervical cancer [ 181 ] and HCC [ 182 ], as well as in metastatic ovarian carcinoma [ 183 ]. These TNFR2 + Tregs exhibit strong suppressive functions [ 184 ] and are associated with a high tumor grade and with a poor prognosis [ 180 , 185 ].…”

“…At the protein level, TNFR2 is upregulated in the TME compared to patient blood in different cancers, such as in NSCLC [ 180 ], cervical cancer [ 181 ] and HCC [ 182 ], as well as in metastatic ovarian carcinoma [ 183 ]. These TNFR2 + Tregs exhibit strong suppressive functions [ 184 ] and are associated with a high tumor grade and with a poor prognosis [ 180 , 185 ]. Moreover, TNF-α produced by stromal cells could participate in the expansion and suppressive function of TA-Tregs.…”