Tissue-resident memory T-cell expressions and their prognostic role in head and neck squamous cell carcinoma: a systematic review and meta-analysis

Abstract Background CD8 + tissue-resident memory T lymphocytes (TRM) are a subset of tumor-infiltrating lymphocytes (TILs) that mediate innate immunity. Clinically, they can prevent tumor development, growth and metastasis and play a potential role in immunosurveillance and long-term immunity in hea...

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Main Authors: Anwar Ali, Muhammad Furqan Bari, Saba Arshad, Mohsin Wahid, Jawad Safdar, Khadija Anwar, Waqas Ahmed Farooqui
Format: Article
Language:English
Published: BMC 2025-02-01
Series:BMC Cancer
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Online Access:https://doi.org/10.1186/s12885-025-13764-2
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author Anwar Ali
Muhammad Furqan Bari
Saba Arshad
Mohsin Wahid
Jawad Safdar
Khadija Anwar
Waqas Ahmed Farooqui
author_facet Anwar Ali
Muhammad Furqan Bari
Saba Arshad
Mohsin Wahid
Jawad Safdar
Khadija Anwar
Waqas Ahmed Farooqui
author_sort Anwar Ali
collection DOAJ
description Abstract Background CD8 + tissue-resident memory T lymphocytes (TRM) are a subset of tumor-infiltrating lymphocytes (TILs) that mediate innate immunity. Clinically, they can prevent tumor development, growth and metastasis and play a potential role in immunosurveillance and long-term immunity in head and neck squamous cell carcinoma (HNSCC). This systematic review and meta-analysis aimed to assess the prognostic significance of CD8 + TRM cells, identified by key immunophenotypic markers CD103, CD69, and CD49a linked to patient outcomes such as overall survival (OS) in HNSCC and its specified subcategory, OSCC. Methods PubMed, Scopus, and Web of Science databases were searched systematically to include original research articles comprising cross-sectional, observational, experimental studies, and clinical trials. The characteristics of the studies were recorded for years of publication, research design, cancer types, HPV status, staging, diagnostic assays, immunophenotypic markers, and immune response regulators. Hazard ratios (HR) with confidence intervals (CI) and p-values were extracted for observing the association between CD103, CD69, and/or CD49a exhibiting CD8 + cytotoxic T lymphocytes with tissue-resident memory potential. The proportion of CD8 + TRM cells co-expressing CD103, CD69, and/or CD49a was estimated by extracting the actual percentage of expression in TME from graphical presentation of data in included studies. Results Among the 276 studies, 11 studies were included by reviewing the abstract or title and full-text articles. The findings of these studies demonstrated a strong association between CD8 + TRM cells, characterized by the expression of CD103, CD69, or CD49a and improved OS in patients with HNSCC, and its subtype, OSCC. Notably, similar trends were observed within the included studies relative to oropharyngeal squamous cell carcinomas (OPSCC), another recognized subtype of HNSCC. The pooled HR was 0.49 (95% CI: 0.23–1.02, p < 0.001), indicating a potential prognostic benefit of CD8 + TRM cell infiltration in HNSCC and related subtypes of OSCC and OPSCC. However, the overall pooled findings at aggregate cancer incidences were not statistically significant (p > 0.05). Conclusion Increased infiltration of CD8 + TRM cells expressing CD103, CD69, and/or CD49a is associated with better prognosis and OS in HNSCC and its subtype, OSCC. Trial Registration This systematic review and meta-analysis were registered in the international database of systematic review protocols at https://www.crd.york.ac.uk/prospero/ under protocol identifier: CRD42024570177.
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spelling doaj-art-6fde474e2d1a423589eba9b42099c80d2025-08-20T02:59:32ZengBMCBMC Cancer1471-24072025-02-0125111610.1186/s12885-025-13764-2Tissue-resident memory T-cell expressions and their prognostic role in head and neck squamous cell carcinoma: a systematic review and meta-analysisAnwar Ali0Muhammad Furqan Bari1Saba Arshad2Mohsin Wahid3Jawad Safdar4Khadija Anwar5Waqas Ahmed Farooqui6Department of Oral and Maxillofacial Surgery, Dr. Ishrat-Ul-Ebad Khan Institute of Oral Health Sciences, Dow University of Health SciencesDepartment of Pathology, Dr. Ishrat-Ul-Ebad Khan Institute of Oral Health Sciences, Dow University of Health SciencesDepartment of Oral Biology, Dr. Ishrat-Ul-Ebad, Khan Institute of Oral Health Sciences, Dow University of Health SciencesDepartment of Pathology, Dow International Medical College, Dow Research Institute of Biotechnology and Biomedical Sciences, Dow University of Health SciencesDepartment of Oral and Maxillofacial Surgery, Dow Dental College, Dow University of Health SciencesDow International Medical College, Dow University of Health SciencesDepartment of Research, School of Public Health, Dow University of Health Sciences KarachiAbstract Background CD8 + tissue-resident memory T lymphocytes (TRM) are a subset of tumor-infiltrating lymphocytes (TILs) that mediate innate immunity. Clinically, they can prevent tumor development, growth and metastasis and play a potential role in immunosurveillance and long-term immunity in head and neck squamous cell carcinoma (HNSCC). This systematic review and meta-analysis aimed to assess the prognostic significance of CD8 + TRM cells, identified by key immunophenotypic markers CD103, CD69, and CD49a linked to patient outcomes such as overall survival (OS) in HNSCC and its specified subcategory, OSCC. Methods PubMed, Scopus, and Web of Science databases were searched systematically to include original research articles comprising cross-sectional, observational, experimental studies, and clinical trials. The characteristics of the studies were recorded for years of publication, research design, cancer types, HPV status, staging, diagnostic assays, immunophenotypic markers, and immune response regulators. Hazard ratios (HR) with confidence intervals (CI) and p-values were extracted for observing the association between CD103, CD69, and/or CD49a exhibiting CD8 + cytotoxic T lymphocytes with tissue-resident memory potential. The proportion of CD8 + TRM cells co-expressing CD103, CD69, and/or CD49a was estimated by extracting the actual percentage of expression in TME from graphical presentation of data in included studies. Results Among the 276 studies, 11 studies were included by reviewing the abstract or title and full-text articles. The findings of these studies demonstrated a strong association between CD8 + TRM cells, characterized by the expression of CD103, CD69, or CD49a and improved OS in patients with HNSCC, and its subtype, OSCC. Notably, similar trends were observed within the included studies relative to oropharyngeal squamous cell carcinomas (OPSCC), another recognized subtype of HNSCC. The pooled HR was 0.49 (95% CI: 0.23–1.02, p < 0.001), indicating a potential prognostic benefit of CD8 + TRM cell infiltration in HNSCC and related subtypes of OSCC and OPSCC. However, the overall pooled findings at aggregate cancer incidences were not statistically significant (p > 0.05). Conclusion Increased infiltration of CD8 + TRM cells expressing CD103, CD69, and/or CD49a is associated with better prognosis and OS in HNSCC and its subtype, OSCC. Trial Registration This systematic review and meta-analysis were registered in the international database of systematic review protocols at https://www.crd.york.ac.uk/prospero/ under protocol identifier: CRD42024570177.https://doi.org/10.1186/s12885-025-13764-2Head and neck cancer squamous cell carcinomaOral squamous cell carcinomaOral cancerTissue resident memoryTRMMeta-analysis
spellingShingle Anwar Ali
Muhammad Furqan Bari
Saba Arshad
Mohsin Wahid
Jawad Safdar
Khadija Anwar
Waqas Ahmed Farooqui
Tissue-resident memory T-cell expressions and their prognostic role in head and neck squamous cell carcinoma: a systematic review and meta-analysis
BMC Cancer
Head and neck cancer squamous cell carcinoma
Oral squamous cell carcinoma
Oral cancer
Tissue resident memory
TRM
Meta-analysis
title Tissue-resident memory T-cell expressions and their prognostic role in head and neck squamous cell carcinoma: a systematic review and meta-analysis
title_full Tissue-resident memory T-cell expressions and their prognostic role in head and neck squamous cell carcinoma: a systematic review and meta-analysis
title_fullStr Tissue-resident memory T-cell expressions and their prognostic role in head and neck squamous cell carcinoma: a systematic review and meta-analysis
title_full_unstemmed Tissue-resident memory T-cell expressions and their prognostic role in head and neck squamous cell carcinoma: a systematic review and meta-analysis
title_short Tissue-resident memory T-cell expressions and their prognostic role in head and neck squamous cell carcinoma: a systematic review and meta-analysis
title_sort tissue resident memory t cell expressions and their prognostic role in head and neck squamous cell carcinoma a systematic review and meta analysis
topic Head and neck cancer squamous cell carcinoma
Oral squamous cell carcinoma
Oral cancer
Tissue resident memory
TRM
Meta-analysis
url https://doi.org/10.1186/s12885-025-13764-2
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