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Infiltrating T-cell markers in cervical carcinogenesis: a systematic review and meta-analysis.

Published version
Peer-reviewed

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Authors

Irvin, Sarah R 
Chornock, Rebecca L 
Sahasrabuddhe, Vikrant V 
Stanley, Margaret 

Abstract

BACKGROUND: The host adaptive immune response helps determine which cervical HPV infections persist and progress to precancer and cancer, and systematic characterisation of T-cell infiltration would help inform key steps in cervical carcinogenesis. METHODS: A systematic review and meta-analysis were conducted of infiltrating T-cells in normal cervix, low-grade lesions, high-grade lesions, and invasive cancers including epithelial, stromal, and total tissue and the following markers: CD3, CD4, CD8, FoxP3, CD25, and the CD4:CD8 ratio. An additional qualitative review summarised longitudinal data on associations between infiltrating T-cells and cervical disease persistence, regression, progression, or prognosis. RESULTS: There were fewer CD3+, CD4+, and CD8+ cells in cervical lesions and more cells in cancers compared to normal epithelium. FoxP3 and CD25+ regulatory T-cell infiltration is high in persistent and precancerous lesions, and longitudinal data show improved outcomes with lower regulatory T-cell levels. CONCLUSIONS: Successful immune evasion may reduce T-cell infiltration in HPV infected and precancerous epithelium, while invasive cancers are highly immunogenic, and regulatory T-cell infiltration increases with cervical disease progression. Understanding these factors may have prognostic value and could aid in novel treatment development and clinical guidelines, but published data are highly heterogeneous and leave important gaps to be filled by future studies.

Description

Funder: Intramural Research Program of the National Cancer Institute at the National Institutes of Health (Z01 CP010124-21).

Keywords

Carcinogenesis, Female, Humans, Lymphocytes, Tumor-Infiltrating, Papillomaviridae, Papillomavirus Infections, T-Lymphocytes, Uterine Cervical Neoplasms

Journal Title

Br J Cancer

Conference Name

Journal ISSN

0007-0920
1532-1827

Volume Title

124

Publisher

Springer Science and Business Media LLC