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Spatial cytotoxic and memory T cells in tumor predict superior survival outcomes in patients with high‐grade serous ovarian cancer

Although the association between tumor‐infiltrating CD3(+) T and CD8(+) T cells and superior survival in high‐grade serous ovarian cancer (HGSOC) has been observed, the different spatial localization of tumor‐infiltrating lymphocytes (TILs) possesses heterogeneous effects. We performed localized mea...

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Autores principales: Zhang, Guodong, Xu, Qing, Zhang, Xiangyun, Yang, Moran, Wang, Yiying, He, Mengdi, Lu, Jiaqi, Liu, Haiou
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209602/
https://www.ncbi.nlm.nih.gov/pubmed/33955198
http://dx.doi.org/10.1002/cam4.3942
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author Zhang, Guodong
Xu, Qing
Zhang, Xiangyun
Yang, Moran
Wang, Yiying
He, Mengdi
Lu, Jiaqi
Liu, Haiou
author_facet Zhang, Guodong
Xu, Qing
Zhang, Xiangyun
Yang, Moran
Wang, Yiying
He, Mengdi
Lu, Jiaqi
Liu, Haiou
author_sort Zhang, Guodong
collection PubMed
description Although the association between tumor‐infiltrating CD3(+) T and CD8(+) T cells and superior survival in high‐grade serous ovarian cancer (HGSOC) has been observed, the different spatial localization of tumor‐infiltrating lymphocytes (TILs) possesses heterogeneous effects. We performed localized measurements in 260 HGSOC from 2 independent cohorts represented in tissue microarray format to determine the localized expression pattern and clinical significance of CD3(+) T, CD8(+) T, and CD45RO(+) cells in HGSOC. Different density of spatial localization of CD3(+) T, CD8(+) T, and CD45RO(+) cells exhibited heterogeneous association with OS. The combination of the center of the tumor and invasive margin localized CD8(+)T cells (CD8(CT&IM)) with the same margin localized CD45RO (CD45RO(CT&IM)) was the most robust prognostic predictor. Immune score (IS) was constructed by integrating FIGO stage with CD8(CT&IM) and CD45RO(IM&CT) and had the best prognostic value in HGSOC. The low‐, intermediate‐, and high‐IS groups were observed in 44.7%, 41.6%, and 13.7% of patients, respectively. Low‐IS identified patients were at higher risk of death compared to high‐IS identified patients (HR = 12.426; 95% CI 5.317–29.039, p < 0.001); meanwhile, we evaluate the RMSTs over 10 years of follow‐up and obtained RMST values of 104.09 months (95% CI 96.31–111.87 months) in the high‐IS group, 75.26 months (95% CI 59.92–90.60 months) in the intermediate‐IS group, and 48.68 months (95%CI 38.82–58.54 months) in the low‐IS group. In general, spatial localization can modulate the clinical effects of TILs in HGSOC. Thus, the spatial expression of CD8 and CD45RO could aid clinicians to determine the follow‐up plan of patients with HGSOC.
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spelling pubmed-82096022021-06-25 Spatial cytotoxic and memory T cells in tumor predict superior survival outcomes in patients with high‐grade serous ovarian cancer Zhang, Guodong Xu, Qing Zhang, Xiangyun Yang, Moran Wang, Yiying He, Mengdi Lu, Jiaqi Liu, Haiou Cancer Med Clinical Cancer Research Although the association between tumor‐infiltrating CD3(+) T and CD8(+) T cells and superior survival in high‐grade serous ovarian cancer (HGSOC) has been observed, the different spatial localization of tumor‐infiltrating lymphocytes (TILs) possesses heterogeneous effects. We performed localized measurements in 260 HGSOC from 2 independent cohorts represented in tissue microarray format to determine the localized expression pattern and clinical significance of CD3(+) T, CD8(+) T, and CD45RO(+) cells in HGSOC. Different density of spatial localization of CD3(+) T, CD8(+) T, and CD45RO(+) cells exhibited heterogeneous association with OS. The combination of the center of the tumor and invasive margin localized CD8(+)T cells (CD8(CT&IM)) with the same margin localized CD45RO (CD45RO(CT&IM)) was the most robust prognostic predictor. Immune score (IS) was constructed by integrating FIGO stage with CD8(CT&IM) and CD45RO(IM&CT) and had the best prognostic value in HGSOC. The low‐, intermediate‐, and high‐IS groups were observed in 44.7%, 41.6%, and 13.7% of patients, respectively. Low‐IS identified patients were at higher risk of death compared to high‐IS identified patients (HR = 12.426; 95% CI 5.317–29.039, p < 0.001); meanwhile, we evaluate the RMSTs over 10 years of follow‐up and obtained RMST values of 104.09 months (95% CI 96.31–111.87 months) in the high‐IS group, 75.26 months (95% CI 59.92–90.60 months) in the intermediate‐IS group, and 48.68 months (95%CI 38.82–58.54 months) in the low‐IS group. In general, spatial localization can modulate the clinical effects of TILs in HGSOC. Thus, the spatial expression of CD8 and CD45RO could aid clinicians to determine the follow‐up plan of patients with HGSOC. John Wiley and Sons Inc. 2021-05-05 /pmc/articles/PMC8209602/ /pubmed/33955198 http://dx.doi.org/10.1002/cam4.3942 Text en © 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Clinical Cancer Research
Zhang, Guodong
Xu, Qing
Zhang, Xiangyun
Yang, Moran
Wang, Yiying
He, Mengdi
Lu, Jiaqi
Liu, Haiou
Spatial cytotoxic and memory T cells in tumor predict superior survival outcomes in patients with high‐grade serous ovarian cancer
title Spatial cytotoxic and memory T cells in tumor predict superior survival outcomes in patients with high‐grade serous ovarian cancer
title_full Spatial cytotoxic and memory T cells in tumor predict superior survival outcomes in patients with high‐grade serous ovarian cancer
title_fullStr Spatial cytotoxic and memory T cells in tumor predict superior survival outcomes in patients with high‐grade serous ovarian cancer
title_full_unstemmed Spatial cytotoxic and memory T cells in tumor predict superior survival outcomes in patients with high‐grade serous ovarian cancer
title_short Spatial cytotoxic and memory T cells in tumor predict superior survival outcomes in patients with high‐grade serous ovarian cancer
title_sort spatial cytotoxic and memory t cells in tumor predict superior survival outcomes in patients with high‐grade serous ovarian cancer
topic Clinical Cancer Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209602/
https://www.ncbi.nlm.nih.gov/pubmed/33955198
http://dx.doi.org/10.1002/cam4.3942
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