Spatial heterogeneity of immune infiltration predicts the prognosis of nasopharyngeal carcinoma patients

Spatial information on the tumor immune microenvironment is of clinical relevance. Here, we aimed to quantify the spatial heterogeneity of lymphocytes and cancer cells and evaluated its prognostic value in patients with nasopharyngeal carcinoma (NPC). The scanned immunohistochemistry images of 336 N...

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Autores principales:	Ya-Qin Wang, Xu Liu, Cheng Xu, Wei Jiang, Shuo-Yu Xu, Yu Zhang, Ye Lin Liang, Jun-Yan Li, Qian Li, Yu-Pei Chen, Yin Zhao, Jing-Ping Yun, Na Liu, Ying-Qin Li, Jun Ma
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	spatial heterogeneity immune hotspot nasopharyngeal carcinoma digital pathology tumor immune microenvironment Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/3b2cae612d8b49b2bf558dfe3e0e8aa3
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spelling	oai:doaj.org-article:3b2cae612d8b49b2bf558dfe3e0e8aa32021-11-04T15:00:45ZSpatial heterogeneity of immune infiltration predicts the prognosis of nasopharyngeal carcinoma patients2162-402X10.1080/2162402X.2021.1976439https://doaj.org/article/3b2cae612d8b49b2bf558dfe3e0e8aa32021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/2162402X.2021.1976439https://doaj.org/toc/2162-402XSpatial information on the tumor immune microenvironment is of clinical relevance. Here, we aimed to quantify the spatial heterogeneity of lymphocytes and cancer cells and evaluated its prognostic value in patients with nasopharyngeal carcinoma (NPC). The scanned immunohistochemistry images of 336 NPC patients from two different hospitals were used to generate cell density maps for tumor and immune cells. Then, Getis-Ord hotspot analysis, a spatial statistic method used to describe species biodiversity in ecological habitats, was applied to identify cancer, immune, and immune-cancer hotspots. The results showed that cancer hotspots were not associated with any of the studied clinical outcomes, while immune-cancer hotspots predicted worse overall survival (OS) in the training cohort. In contrast, a high immune hotspot score was significantly associated with better OS (HR 0.41, 95% CI 0.22–0.77, P = .006), disease-free survival (DFS) (HR 0.43, 95% CI 0.24–0.75, P = .003) and distant metastasis-free survival (DMFS) (HR 0.40, 95% CI 0.20–0.81, P = .011) in NPC patients in the training cohort, and similar associations were also evident in the validation cohort. Importantly, multivariate analysis revealed that the immune hotspot score remained an independent prognostic indicator for OS, DFS, and DMFS in both cohorts. We explored the spatial heterogeneity of cancer cells and lymphocytes in the tumor microenvironment of NPC patients using digital pathology and ecological analysis methods and further constructed three spatial scores. Our study demonstrates that spatial variation may aid in the identification of the clinical prognosis of NPC patients, but further investigation is needed.Ya-Qin WangXu LiuCheng XuWei JiangShuo-Yu XuYu ZhangYe Lin LiangJun-Yan LiQian LiYu-Pei ChenYin ZhaoJing-Ping YunNa LiuYing-Qin LiJun MaTaylor & Francis Grouparticlespatial heterogeneityimmune hotspotnasopharyngeal carcinomadigital pathologytumor immune microenvironmentImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENOncoImmunology, Vol 10, Iss 1 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	spatial heterogeneity immune hotspot nasopharyngeal carcinoma digital pathology tumor immune microenvironment Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	spatial heterogeneity immune hotspot nasopharyngeal carcinoma digital pathology tumor immune microenvironment Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Ya-Qin Wang Xu Liu Cheng Xu Wei Jiang Shuo-Yu Xu Yu Zhang Ye Lin Liang Jun-Yan Li Qian Li Yu-Pei Chen Yin Zhao Jing-Ping Yun Na Liu Ying-Qin Li Jun Ma Spatial heterogeneity of immune infiltration predicts the prognosis of nasopharyngeal carcinoma patients
description	Spatial information on the tumor immune microenvironment is of clinical relevance. Here, we aimed to quantify the spatial heterogeneity of lymphocytes and cancer cells and evaluated its prognostic value in patients with nasopharyngeal carcinoma (NPC). The scanned immunohistochemistry images of 336 NPC patients from two different hospitals were used to generate cell density maps for tumor and immune cells. Then, Getis-Ord hotspot analysis, a spatial statistic method used to describe species biodiversity in ecological habitats, was applied to identify cancer, immune, and immune-cancer hotspots. The results showed that cancer hotspots were not associated with any of the studied clinical outcomes, while immune-cancer hotspots predicted worse overall survival (OS) in the training cohort. In contrast, a high immune hotspot score was significantly associated with better OS (HR 0.41, 95% CI 0.22–0.77, P = .006), disease-free survival (DFS) (HR 0.43, 95% CI 0.24–0.75, P = .003) and distant metastasis-free survival (DMFS) (HR 0.40, 95% CI 0.20–0.81, P = .011) in NPC patients in the training cohort, and similar associations were also evident in the validation cohort. Importantly, multivariate analysis revealed that the immune hotspot score remained an independent prognostic indicator for OS, DFS, and DMFS in both cohorts. We explored the spatial heterogeneity of cancer cells and lymphocytes in the tumor microenvironment of NPC patients using digital pathology and ecological analysis methods and further constructed three spatial scores. Our study demonstrates that spatial variation may aid in the identification of the clinical prognosis of NPC patients, but further investigation is needed.
format	article
author	Ya-Qin Wang Xu Liu Cheng Xu Wei Jiang Shuo-Yu Xu Yu Zhang Ye Lin Liang Jun-Yan Li Qian Li Yu-Pei Chen Yin Zhao Jing-Ping Yun Na Liu Ying-Qin Li Jun Ma
author_facet	Ya-Qin Wang Xu Liu Cheng Xu Wei Jiang Shuo-Yu Xu Yu Zhang Ye Lin Liang Jun-Yan Li Qian Li Yu-Pei Chen Yin Zhao Jing-Ping Yun Na Liu Ying-Qin Li Jun Ma
author_sort	Ya-Qin Wang
title	Spatial heterogeneity of immune infiltration predicts the prognosis of nasopharyngeal carcinoma patients
title_short	Spatial heterogeneity of immune infiltration predicts the prognosis of nasopharyngeal carcinoma patients
title_full	Spatial heterogeneity of immune infiltration predicts the prognosis of nasopharyngeal carcinoma patients
title_fullStr	Spatial heterogeneity of immune infiltration predicts the prognosis of nasopharyngeal carcinoma patients
title_full_unstemmed	Spatial heterogeneity of immune infiltration predicts the prognosis of nasopharyngeal carcinoma patients
title_sort	spatial heterogeneity of immune infiltration predicts the prognosis of nasopharyngeal carcinoma patients
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/3b2cae612d8b49b2bf558dfe3e0e8aa3
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Spatial heterogeneity of immune infiltration predicts the prognosis of nasopharyngeal carcinoma patients

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