Prognostic Significance of CD4+ and CD8+ Tumor-Infiltrating Lymphocytes in Head and Neck Squamous Cell Carcinoma: A Meta-Analysis
Objective: It has been suggested that the presence of tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment is associated with a better prognosis in different types of cancer. In this systematic review and meta-analysis, we investigated the prognostic role of CD4+ and CD8+ TILs in head...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-02-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/13/4/781 |
| _version_ | 1797396640033669120 |
|---|---|
| author | Daniele Borsetto Michele Tomasoni Karl Payne Jerry Polesel Alberto Deganello Paolo Bossi James R. Tysome Liam Masterson Giancarlo Tirelli Margherita Tofanelli Paolo Boscolo-Rizzo |
| author_facet | Daniele Borsetto Michele Tomasoni Karl Payne Jerry Polesel Alberto Deganello Paolo Bossi James R. Tysome Liam Masterson Giancarlo Tirelli Margherita Tofanelli Paolo Boscolo-Rizzo |
| author_sort | Daniele Borsetto |
| collection | DOAJ |
| description | Objective: It has been suggested that the presence of tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment is associated with a better prognosis in different types of cancer. In this systematic review and meta-analysis, we investigated the prognostic role of CD4+ and CD8+ TILs in head and neck squamous cell carcinoma (HNSCC). Methods: PubMed, Cochrane, Embase, Scopus, and Web of Science were searched up to September 2020. This study was conducted following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) checklist. Risk ratios from individual studies were displayed in forest plots and the pooled hazard ratios (HR) of death and corresponding confidence intervals (CI) were calculated according to random-effects models. Risk of bias of the included studies was assessed through the Newcastle–Ottawa scale. Results: 28 studies met the inclusion criteria. Studies conducted on HNSCC subsites combined reported a significant reduction in the risk of death for both high CD4+ (HR: 0.77; 95% CI: 0.65–0.93) and high CD8+ TILs (HR: 0.64; 95% CI: 0.47–0.88). High CD4+ TILs were associated with significantly better overall survival among oropharyngeal HNSCC (HR: 0.52; 95% CI: 0.31–0.89), as well as high CD8+ TILS in Human papillomavirus −ve and +ve cancers (HR: 0.39; 95% CI: 0.16–0.93 and HR: 0.40; 95% CI 0.21–0.76 respectively). CD8+ TILs were also associated with improved survival in hypopharyngeal cancers (HR = 0.43 CI: 0.30–0.63). No significant association emerged for patients with cancer of the oral cavity or larynx. Conclusions: The findings from this meta-analysis demonstrate the prognostic significance of CD8+ and CD4+ TILs in HNSCC and variation in tumor subsite warrants further focused investigation. We highlight how TILs may serve as predictive biomarkers to risk stratify patients into treatment groups, with applications in immune-checkpoint inhibitors notable areas for further research. |
| first_indexed | 2024-03-09T00:54:18Z |
| format | Article |
| id | doaj.art-3514c009e8b14ff29b1bd12e9b24ae29 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T00:54:18Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-3514c009e8b14ff29b1bd12e9b24ae292023-12-11T16:57:47ZengMDPI AGCancers2072-66942021-02-0113478110.3390/cancers13040781Prognostic Significance of CD4+ and CD8+ Tumor-Infiltrating Lymphocytes in Head and Neck Squamous Cell Carcinoma: A Meta-AnalysisDaniele Borsetto0Michele Tomasoni1Karl Payne2Jerry Polesel3Alberto Deganello4Paolo Bossi5James R. Tysome6Liam Masterson7Giancarlo Tirelli8Margherita Tofanelli9Paolo Boscolo-Rizzo10Department of ENT, Addenbrookes’ Hospital, Cambridge University Hospital Trust, Cambridge CB2 0QQ, UKOtorhinolaryngology-Head and Neck Surgery, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, 25123 Brescia, ItalyInstitute of Head and Neck Studies and Education, University of Birmingham, Birmingham B15 2TT, UKUnit of Cancer Epidemiology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, ItalyOtorhinolaryngology-Head and Neck Surgery, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, 25123 Brescia, ItalyMedical Oncology Unit, Department of Medical Oncology, ASST Spedali Civili di Brescia, 25123 Brescia, ItalyDepartment of ENT, Addenbrookes’ Hospital, Cambridge University Hospital Trust, Cambridge CB2 0QQ, UKDepartment of ENT, Addenbrookes’ Hospital, Cambridge University Hospital Trust, Cambridge CB2 0QQ, UKDepartment of Medical, Surgical and Health Sciences, Section of Otolaryngology, University of Trieste, 34149 Trieste, ItalyDepartment of Medical, Surgical and Health Sciences, Section of Otolaryngology, University of Trieste, 34149 Trieste, ItalyDepartment of Medical, Surgical and Health Sciences, Section of Otolaryngology, University of Trieste, 34149 Trieste, ItalyObjective: It has been suggested that the presence of tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment is associated with a better prognosis in different types of cancer. In this systematic review and meta-analysis, we investigated the prognostic role of CD4+ and CD8+ TILs in head and neck squamous cell carcinoma (HNSCC). Methods: PubMed, Cochrane, Embase, Scopus, and Web of Science were searched up to September 2020. This study was conducted following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) checklist. Risk ratios from individual studies were displayed in forest plots and the pooled hazard ratios (HR) of death and corresponding confidence intervals (CI) were calculated according to random-effects models. Risk of bias of the included studies was assessed through the Newcastle–Ottawa scale. Results: 28 studies met the inclusion criteria. Studies conducted on HNSCC subsites combined reported a significant reduction in the risk of death for both high CD4+ (HR: 0.77; 95% CI: 0.65–0.93) and high CD8+ TILs (HR: 0.64; 95% CI: 0.47–0.88). High CD4+ TILs were associated with significantly better overall survival among oropharyngeal HNSCC (HR: 0.52; 95% CI: 0.31–0.89), as well as high CD8+ TILS in Human papillomavirus −ve and +ve cancers (HR: 0.39; 95% CI: 0.16–0.93 and HR: 0.40; 95% CI 0.21–0.76 respectively). CD8+ TILs were also associated with improved survival in hypopharyngeal cancers (HR = 0.43 CI: 0.30–0.63). No significant association emerged for patients with cancer of the oral cavity or larynx. Conclusions: The findings from this meta-analysis demonstrate the prognostic significance of CD8+ and CD4+ TILs in HNSCC and variation in tumor subsite warrants further focused investigation. We highlight how TILs may serve as predictive biomarkers to risk stratify patients into treatment groups, with applications in immune-checkpoint inhibitors notable areas for further research.https://www.mdpi.com/2072-6694/13/4/781head and neck cancertumor-infiltrating lymphocyteprognosisTILcancer |
| spellingShingle | Daniele Borsetto Michele Tomasoni Karl Payne Jerry Polesel Alberto Deganello Paolo Bossi James R. Tysome Liam Masterson Giancarlo Tirelli Margherita Tofanelli Paolo Boscolo-Rizzo Prognostic Significance of CD4+ and CD8+ Tumor-Infiltrating Lymphocytes in Head and Neck Squamous Cell Carcinoma: A Meta-Analysis Cancers head and neck cancer tumor-infiltrating lymphocyte prognosis TIL cancer |
| title | Prognostic Significance of CD4+ and CD8+ Tumor-Infiltrating Lymphocytes in Head and Neck Squamous Cell Carcinoma: A Meta-Analysis |
| title_full | Prognostic Significance of CD4+ and CD8+ Tumor-Infiltrating Lymphocytes in Head and Neck Squamous Cell Carcinoma: A Meta-Analysis |
| title_fullStr | Prognostic Significance of CD4+ and CD8+ Tumor-Infiltrating Lymphocytes in Head and Neck Squamous Cell Carcinoma: A Meta-Analysis |
| title_full_unstemmed | Prognostic Significance of CD4+ and CD8+ Tumor-Infiltrating Lymphocytes in Head and Neck Squamous Cell Carcinoma: A Meta-Analysis |
| title_short | Prognostic Significance of CD4+ and CD8+ Tumor-Infiltrating Lymphocytes in Head and Neck Squamous Cell Carcinoma: A Meta-Analysis |
| title_sort | prognostic significance of cd4 and cd8 tumor infiltrating lymphocytes in head and neck squamous cell carcinoma a meta analysis |
| topic | head and neck cancer tumor-infiltrating lymphocyte prognosis TIL cancer |
| url | https://www.mdpi.com/2072-6694/13/4/781 |
| work_keys_str_mv | AT danieleborsetto prognosticsignificanceofcd4andcd8tumorinfiltratinglymphocytesinheadandnecksquamouscellcarcinomaametaanalysis AT micheletomasoni prognosticsignificanceofcd4andcd8tumorinfiltratinglymphocytesinheadandnecksquamouscellcarcinomaametaanalysis AT karlpayne prognosticsignificanceofcd4andcd8tumorinfiltratinglymphocytesinheadandnecksquamouscellcarcinomaametaanalysis AT jerrypolesel prognosticsignificanceofcd4andcd8tumorinfiltratinglymphocytesinheadandnecksquamouscellcarcinomaametaanalysis AT albertodeganello prognosticsignificanceofcd4andcd8tumorinfiltratinglymphocytesinheadandnecksquamouscellcarcinomaametaanalysis AT paolobossi prognosticsignificanceofcd4andcd8tumorinfiltratinglymphocytesinheadandnecksquamouscellcarcinomaametaanalysis AT jamesrtysome prognosticsignificanceofcd4andcd8tumorinfiltratinglymphocytesinheadandnecksquamouscellcarcinomaametaanalysis AT liammasterson prognosticsignificanceofcd4andcd8tumorinfiltratinglymphocytesinheadandnecksquamouscellcarcinomaametaanalysis AT giancarlotirelli prognosticsignificanceofcd4andcd8tumorinfiltratinglymphocytesinheadandnecksquamouscellcarcinomaametaanalysis AT margheritatofanelli prognosticsignificanceofcd4andcd8tumorinfiltratinglymphocytesinheadandnecksquamouscellcarcinomaametaanalysis AT paoloboscolorizzo prognosticsignificanceofcd4andcd8tumorinfiltratinglymphocytesinheadandnecksquamouscellcarcinomaametaanalysis |