Understanding the impact of chemotherapy on the immune landscape of high-grade serous ovarian cancer
Objectives: We quantitatively characterized the change in temporospatial expression of repressive and stimulatory checkpoints across immune cell populations in the tumor microenvironment in a cohort of high grade serous ovarian carcinomas (HGSOC) using matched samples before and after neoadjuvant pl...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-02-01
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| Series: | Gynecologic Oncology Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352578922000066 |
| _version_ | 1819205524920467456 |
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| author | Rami Vanguri Jamal Benhamida Jonathan H. Young Yanyun Li Oliver Zivanovic Dennis Chi Alexandra Snyder Travis J. Hollmann Katherine L. Mager |
| author_facet | Rami Vanguri Jamal Benhamida Jonathan H. Young Yanyun Li Oliver Zivanovic Dennis Chi Alexandra Snyder Travis J. Hollmann Katherine L. Mager |
| author_sort | Rami Vanguri |
| collection | DOAJ |
| description | Objectives: We quantitatively characterized the change in temporospatial expression of repressive and stimulatory checkpoints across immune cell populations in the tumor microenvironment in a cohort of high grade serous ovarian carcinomas (HGSOC) using matched samples before and after neoadjuvant platinum-based chemotherapy. Methods: Using retrospectively collected matched tissue samples from 9 patients, cell populations were assessed using multiplex immunofluorescence using the Vectra Multispectral Imaging System (Perkin Elmer). We used multiple panels to assess: tumor (AE1/AE3), T cells (CD3, CD8, FOXP3), macrophages (CD68) as well as immune checkpoints (C3aR, PD-1, PD-L1, LAG3, IDO, ICOS, GITR). IHC staining was performed for folate receptor status. Changes in immune cell populations as well as intensities of associated repressive and stimulatory proteins were assessed pre- to post-treatment. Results: We observed a consistently high pre-treatment stromal macrophage population which is reduced post-chemotherapy with post-treatment enrichment in macrophage PD-L1 expression. While inhibitory checkpoint expression on T cells was heterogeneous post-chemotherapy, we observed a change in the ThICOS+:Treg ratio which resulted in ThICOS+ cells outnumbering Treg cells post-treatment. Spatial analysis revealed the proximity of Treg cells to ThICOS+ T cells decreased post-treatment. We also observed upward shifts in Teff:Treg T cell ratios with retention of immune checkpoints PD-1, LAG3 and GITR. Conclusions: In this unique dataset of pre and post matched chemotherapy treated HGSOC patients, we observed changes in immune cell subsets expressing repressive or stimulatory proteins resulting in immune compositions more favorable to checkpoint modulations, suggesting novel therapeutic strategies in the recurrent setting. |
| first_indexed | 2024-12-23T04:53:05Z |
| format | Article |
| id | doaj.art-aca89ed109ab4ad5b29c290f13a08bce |
| institution | Directory Open Access Journal |
| issn | 2352-5789 |
| language | English |
| last_indexed | 2024-12-23T04:53:05Z |
| publishDate | 2022-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Gynecologic Oncology Reports |
| spelling | doaj.art-aca89ed109ab4ad5b29c290f13a08bce2022-12-21T17:59:24ZengElsevierGynecologic Oncology Reports2352-57892022-02-0139100926Understanding the impact of chemotherapy on the immune landscape of high-grade serous ovarian cancerRami Vanguri0Jamal Benhamida1Jonathan H. Young2Yanyun Li3Oliver Zivanovic4Dennis Chi5Alexandra Snyder6Travis J. Hollmann7Katherine L. Mager8Computational Oncology Service, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USADepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USASchool of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USADepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USAGynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USAGynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USADepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USADepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY, USADepartment of Gynecologic Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA; Corresponding authors at: Roswell Park Comprehensive Cancer Center, Elm and Carlton Streets, Buffalo, NY 14263, USA.Objectives: We quantitatively characterized the change in temporospatial expression of repressive and stimulatory checkpoints across immune cell populations in the tumor microenvironment in a cohort of high grade serous ovarian carcinomas (HGSOC) using matched samples before and after neoadjuvant platinum-based chemotherapy. Methods: Using retrospectively collected matched tissue samples from 9 patients, cell populations were assessed using multiplex immunofluorescence using the Vectra Multispectral Imaging System (Perkin Elmer). We used multiple panels to assess: tumor (AE1/AE3), T cells (CD3, CD8, FOXP3), macrophages (CD68) as well as immune checkpoints (C3aR, PD-1, PD-L1, LAG3, IDO, ICOS, GITR). IHC staining was performed for folate receptor status. Changes in immune cell populations as well as intensities of associated repressive and stimulatory proteins were assessed pre- to post-treatment. Results: We observed a consistently high pre-treatment stromal macrophage population which is reduced post-chemotherapy with post-treatment enrichment in macrophage PD-L1 expression. While inhibitory checkpoint expression on T cells was heterogeneous post-chemotherapy, we observed a change in the ThICOS+:Treg ratio which resulted in ThICOS+ cells outnumbering Treg cells post-treatment. Spatial analysis revealed the proximity of Treg cells to ThICOS+ T cells decreased post-treatment. We also observed upward shifts in Teff:Treg T cell ratios with retention of immune checkpoints PD-1, LAG3 and GITR. Conclusions: In this unique dataset of pre and post matched chemotherapy treated HGSOC patients, we observed changes in immune cell subsets expressing repressive or stimulatory proteins resulting in immune compositions more favorable to checkpoint modulations, suggesting novel therapeutic strategies in the recurrent setting.http://www.sciencedirect.com/science/article/pii/S2352578922000066Ovarian cancerTumor microenvironmentImmunotherapy |
| spellingShingle | Rami Vanguri Jamal Benhamida Jonathan H. Young Yanyun Li Oliver Zivanovic Dennis Chi Alexandra Snyder Travis J. Hollmann Katherine L. Mager Understanding the impact of chemotherapy on the immune landscape of high-grade serous ovarian cancer Gynecologic Oncology Reports Ovarian cancer Tumor microenvironment Immunotherapy |
| title | Understanding the impact of chemotherapy on the immune landscape of high-grade serous ovarian cancer |
| title_full | Understanding the impact of chemotherapy on the immune landscape of high-grade serous ovarian cancer |
| title_fullStr | Understanding the impact of chemotherapy on the immune landscape of high-grade serous ovarian cancer |
| title_full_unstemmed | Understanding the impact of chemotherapy on the immune landscape of high-grade serous ovarian cancer |
| title_short | Understanding the impact of chemotherapy on the immune landscape of high-grade serous ovarian cancer |
| title_sort | understanding the impact of chemotherapy on the immune landscape of high grade serous ovarian cancer |
| topic | Ovarian cancer Tumor microenvironment Immunotherapy |
| url | http://www.sciencedirect.com/science/article/pii/S2352578922000066 |
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