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Updated: Aug 8, 2025
Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
TNFR2 expression predicts the responses to immune checkpoint inhibitor treatments
Ping Liao1, Mengmeng Jiang1, Md Sahidul Islam1
1Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macao, Macao SAR, China.
Abstract:
Immune checkpoint inhibitors (ICIs) by targeting PD-1/PD-L1 or CTLA-4 have markedly improved the outcome of cancer patients. However, most solid tumor patients can't benefit from such therapy. Identification of novel biomarkers to predict the responses of ICIs is crucial to enhance their therapeutic efficacy. TNFR2 is highly expressed by the maximally immunosuppressive subset of CD4+Foxp3+ regulatory T cells (Tregs), especially those present in tumor microenvironment (TME). Since Tregs represent a major cellular mechanism in tumor immune evasion, TNFR2 may be a useful biomarker to predict the responses to ICIs therapy. This notion is supported by our analysis of the computational tumor immune dysfunction and exclusion (TIDE) framework from published single-cell RNA-seq data of pan-cancer databases. The results show that, as expected, TNFR2 is highly expressed by tumor-infiltrating Tregs. Interestingly, TNFR2 is also expressed by the exhausted CD8 T cells in breast cancer (BRCA), hepatocellular carcinoma (HCC), lung squamous cell carcinoma (LUSC), and melanoma (MELA). Importantly, high expression of TNFR2 is associated with poor responses to the treatment with ICIs in BRCA, HCC, LUSC, and MELA. In conclusion, the expression of TNFR2 in TME may be a reliable biomarker for the precision of ICIs treatment of cancer patients, and this idea merits further research.
Insights
Tumor necrosis factor receptor 2 (TNFR2) is highly expressed in the tumor microenvironment (TME) and may predict poor responses to immune checkpoint inhibitors (ICIs). This finding could lead to better patient selection for cancer immunotherapy.
Area of Science:
- Immunology
- Oncology
- Biomarker Discovery
Background:
- Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 or CTLA-4 have improved cancer patient outcomes.
- However, many solid tumor patients do not benefit from ICIs, necessitating new biomarkers for predicting treatment response.
- Regulatory T cells (Tregs), particularly those expressing TNFR2 in the tumor microenvironment (TME), are key players in tumor immune evasion.
Purpose of the Study:
- To investigate the potential of Tumor Necrosis Factor Receptor 2 (TNFR2) as a predictive biomarker for immune checkpoint inhibitor (ICI) therapy response.
- To analyze TNFR2 expression in tumor-infiltrating cells and its association with ICI treatment outcomes across various cancers.
Main Methods:
- Utilized the computational Tumor Immune Dysfunction and Exclusion (TIDE) framework.
- Analyzed publicly available single-cell RNA-sequencing data from pan-cancer databases.
- Correlated TNFR2 expression levels with clinical responses to ICI therapy in specific cancer types.
Main Results:
- TNFR2 is highly expressed by tumor-infiltrating Tregs across multiple cancers.
- TNFR2 is also found on exhausted CD8 T cells in breast cancer (BRCA), hepatocellular carcinoma (HCC), lung squamous cell carcinoma (LUSC), and melanoma (MELA).
- Elevated TNFR2 expression is significantly associated with poor responses to ICIs in BRCA, HCC, LUSC, and MELA.
Conclusions:
- TNFR2 expression within the TME may serve as a reliable biomarker for predicting patient response to ICIs.
- This research suggests TNFR2's potential utility in precision medicine for cancer immunotherapy.
- Further investigation is warranted to validate TNFR2 as a predictive biomarker for ICI treatment efficacy.
