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Baseline immunity and impact of chemotherapy on immune microenvironment in cervical cancer.
- Source :
-
British journal of cancer [Br J Cancer] 2021 Jan; Vol. 124 (2), pp. 414-424. Date of Electronic Publication: 2020 Oct 22. - Publication Year :
- 2021
-
Abstract
- Background: 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.<br />Methods: 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.<br />Results: 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.<br />Conclusions: 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.
- Subjects :
- Adult
Aged
Aged, 80 and over
Carcinoma drug therapy
Carcinoma immunology
Carcinoma pathology
Chemotherapy, Adjuvant methods
Cohort Studies
Female
Humans
Lymphocytes, Tumor-Infiltrating drug effects
Middle Aged
Neoadjuvant Therapy methods
Retrospective Studies
Tumor Microenvironment drug effects
Uterine Cervical Neoplasms pathology
Antineoplastic Agents therapeutic use
Lymphocytes, Tumor-Infiltrating immunology
Tumor Microenvironment immunology
Uterine Cervical Neoplasms drug therapy
Uterine Cervical Neoplasms immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1532-1827
- Volume :
- 124
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- British journal of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 33087896
- Full Text :
- https://doi.org/10.1038/s41416-020-01123-w