Dataset Information

Circulating CD8⁺ mucosal-associated invariant T cells correlate with improved treatment responses and overall survival in anti-PD-1-treated melanoma patients.

ABSTRACT:

Objectives

While much of the research concerning factors associated with responses to immune checkpoint inhibitors (ICIs) has focussed on the contributions of conventional peptide-specific T cells, the role of unconventional T cells, such as mucosal-associated invariant T (MAIT) cells, in human melanoma remains largely unknown. MAIT cells are an abundant population of innate-like T cells expressing a semi-invariant T-cell receptor restricted to the MHC class I-like molecule, MR1, presenting vitamin B metabolites derived from bacteria. We sought to characterise MAIT cells in melanoma patients and determined their association with treatment responses and clinical outcomes.

Methods

In this prospective clinical study, we analysed the frequency and functional profile of circulating and tumor-infiltrating MAIT cells in human melanoma patients. Using flow cytometry, we compared these across metastatic sites and between ICI responders vs. non-responders as well as healthy donors.

Results

We identified tumor-infiltrating MAIT cells in melanomas across metastatic sites and found that the number of circulating MAIT cells is reduced in melanoma patients compared to healthy donors. However, circulating MAIT cell frequencies are restored by ICI treatment in responding patients, correlating with treatment responses, in which patients with high frequencies of MAIT cells exhibited significantly improved overall survival.

Conclusion

Our results suggest that MAIT cells may be a potential predictive marker of responses to immunotherapies and provide rationale for testing MAIT cell-directed therapies in combination with current and next-generation ICIs.

SUBMITTER: Vorwald VM

PROVIDER: S-EPMC8743567 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeTo identify CD8+ T lymphocyte-related coexpressed genes that increase CD8+ T lymphocyte proportions in breast cancer and to elucidate the underlying mechanisms among relevant genes in the tumor microenvironment.MethodWe obtained breast cancer expression matrix data and patient phenotype following information from TCGA-BRCA FPKM. Tumor purity, immune score, stromal score, and estimate score were calculated using the estimate package in R. The CD8+ T lymphocyte proportions in each breast carcinoma sample were estimated using the CIBERSORT algorithm. The samples with p < 0.05 were considered to be significant and were taken into the weighted gene coexpression network analysis. Based on the CD8+ T lymphocyte proportion and tumor purity, we generated CD8+ T lymphocyte coexpression networks and selected the most CD8+ T lymphocyte-related module as our interested coexpression modules. We constructed a CD8+ T cell model based on the least absolute shrinkage and selection operator method (LASSO) regression model and robust model and evaluate the prediction ability in different subgroups.ResultsA breast carcinoma CD8+ T lymphocyte proportion coexpression yellow module was determined. The coexpression genes in the yellow module were determined to increase the CD8+ T lymphocyte proportion levels in breast cancer patients. The yellow module was significantly enriched in the antigen presentation process, cellular response to interferon-gamma, and leukocyte proliferation. Subsequently, we generated CD8+ T cell-related genes lasso regression risk model and robust model, and eight genes were taken into the risk model. The risk score showed significant prognostic ability in various subgroups. Expression levels of proteins, encoded by CD74, were lower in the breast carcinoma samples than in normal tissue, suggesting expression differences at both the mRNA and the protein levels.ConclusionThese eight CD8+ T lymphocyte proportion coexpression genes increase CD8+ T lymphocyte in breast cancer by an antigen presentation process. The mechanism might suggest new pathways to improve outcomes in patients who do not benefit from immune therapy.

Dataset Information

Circulating CD8⁺ mucosal-associated invariant T cells correlate with improved treatment responses and overall survival in anti-PD-1-treated melanoma patients.

Objectives

Methods

Results

Conclusion

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OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Circulating CD8+ mucosal-associated invariant T cells correlate with improved treatment responses and overall survival in anti-PD-1-treated melanoma patients.

Objectives

Methods

Results

Conclusion

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Circulating CD8⁺ mucosal-associated invariant T cells correlate with improved treatment responses and overall survival in anti-PD-1-treated melanoma patients.