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Baseline immunity and impact of chemotherapy on immune microenvironment in cervical cancer.

Authors :
Zhang, Yi
Yu, Minhua
Jing, Ying
Cheng, Jiejun
Zhang, Caiyan
Cheng, Lin
Lu, Haijiao
Cai, Mei-Chun
Wu, Jie
Wang, Wenjing
Lou, Weihua
Qiu, Lihua
Tan, Li
Lu, Huaiwu
Yin, Xia
Zhuang, Guanglei
Di, Wen
Source :
British Journal of Cancer; 2021, Vol. 124 Issue 2, p414-424, 11p
Publication Year :
2021

Abstract

<bold>Background: </bold>We aimed to comprehensively evaluate the immunologic landscape at baseline and upon chemotherapy in cervical cancer. The information should aid ongoing clinical investigations of checkpoint blockade immunotherapies in this disease setting.<bold>Methods: </bold>A series of 109 cervical carcinoma patients was retrospectively assayed before and after neoadjuvant chemotherapy. Tumour-infiltrating immune markers (CD3, CD4, CD8, CD20, CD56, CD68, PD-1, PD-L1) were assessed by immunohistochemistry. RNA sequencing analysis was performed on matched pre- and post-treatment fresh-frozen tissues.<bold>Results: </bold>At diagnosis, diverse immune cell types including CD20+ B cells, CD3+ T cells, CD56+ natural killer (NK) cells, and CD68+ macrophages were detected in different proportions of cervical carcinoma. Unsupervised hierarchical clustering evidently showed that CD4+ and CD8+ T cell abundance correlated with PD-L1 expression. Based on the immune infiltration patterns, the patients could be stratified into four groups with prognostic relevance, namely, 'immuno-active', 'immuno-medial', 'immuno-NK', and 'immuno-deficient'. Neoadjuvant chemotherapy was associated with increased CD4, CD8, CD20, and CD56 signals, most prominently in good responders. Transcriptomic data corroborated the improved anticancer immunity and identified immunosuppressive CD200 upregulation following chemotherapeutic intervention.<bold>Conclusions: </bold>A subset of cervical cancer harbours active immune microenvironment, and chemotherapy treatment may further exert locoregional immunostimulation. Immune checkpoint inhibitors as combination or maintenance therapies warrant future exploration in clinic. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00070920
Volume :
124
Issue :
2
Database :
Complementary Index
Journal :
British Journal of Cancer
Publication Type :
Academic Journal
Accession number :
148072550
Full Text :
https://doi.org/10.1038/s41416-020-01123-w