Prognostic implications of immune classification based on PD-L1 expression and tumor-infiltrating lymphocytes in endocervical adenocarcinoma

Background: Endocervical adenocarcinoma (ECA) comprises a heterogeneous group of diseases whose incidence has increased significantly in recent decades. ECA can be histologically classified into human papillomavirus-associated (HPVA) and non-HPVA (NHPVA) types. Given the variability in pathological...

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Main Authors: Li-Jun Wei, Zi-Yun Wu, Li-Yan Wu, Ying-Wen Wu, Hao-Yu Liang, Rong-Zhen Luo, Li-Li Liu
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Translational Oncology
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Online Access:http://www.sciencedirect.com/science/article/pii/S1936523324003917
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author Li-Jun Wei
Zi-Yun Wu
Li-Yan Wu
Ying-Wen Wu
Hao-Yu Liang
Rong-Zhen Luo
Li-Li Liu
author_facet Li-Jun Wei
Zi-Yun Wu
Li-Yan Wu
Ying-Wen Wu
Hao-Yu Liang
Rong-Zhen Luo
Li-Li Liu
author_sort Li-Jun Wei
collection DOAJ
description Background: Endocervical adenocarcinoma (ECA) comprises a heterogeneous group of diseases whose incidence has increased significantly in recent decades. ECA can be histologically classified into human papillomavirus-associated (HPVA) and non-HPVA (NHPVA) types. Given the variability in pathological features and clinical behavior between the subtypes, evaluating their respective immune microenvironments is essential. They can be categorized into distinct tumor microenvironment immune types (TMIT). Methods: A total of 540 surgically resected ECA samples were classified into HPVA and NHPVA subgroups. Tumor-infiltrating immune markers were assessed using immunohistochemistry. We categorized ECA into four TMIT based on PD-L1 and CD8+ tumor-infiltrating lymphocytes (TILs) expression, and analyzed their prognostic significance. Results: PD-L1 positivity was observed in 319 out of 464 (68.8%) HPVA and 55 out of 76 (72.4%) NHPVA. Across the entire cohort, high CD8+ TILs expression was significantly associated with improved disease-free survival (DFS, p=0.018) and overall survival (OS, p=0.031). A total of 177 samples (32.8%) were classified as TMIT I (high PD-L1 and high CD8+ TILs), exhibiting markedly denser immune cell infiltration compared to the other TMIT groups. In NHPVA subgroup, TMIT was significantly associated with both DFS (p=0.005) and OS (p=0.003). Multivariate analysis identified TMIT as an independent prognostic factor for DFS in the NHPVA group, with TMIT I indicating a more favorable prognosis (p=0.042). Conclusions: TMIT I group within the NHPVA population is most likely to benefit from PD-L1/PD-1 blockade immunotherapies. The immune classification of ECA demonstrates significant prognostic value, suggesting its potential utility in guiding clinical stratification and therapeutic decision-making.
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spelling doaj-art-472925391cb54aa5844ae177ed596edb2025-01-22T05:41:33ZengElsevierTranslational Oncology1936-52332025-02-0152102265Prognostic implications of immune classification based on PD-L1 expression and tumor-infiltrating lymphocytes in endocervical adenocarcinomaLi-Jun Wei0Zi-Yun Wu1Li-Yan Wu2Ying-Wen Wu3Hao-Yu Liang4Rong-Zhen Luo5Li-Li Liu6Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China; Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, ChinaDepartment of Urology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, ChinaSun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China; Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, ChinaSun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China; Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, ChinaSun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China; Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, ChinaSun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China; Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China; Corresponding authors at: Department of Pathology, Sun Yat-sen University Cancer Center, 651# Dong Feng Road East, Guangzhou, 510060, Guangdong, China.Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China; Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China; Corresponding authors at: Department of Pathology, Sun Yat-sen University Cancer Center, 651# Dong Feng Road East, Guangzhou, 510060, Guangdong, China.Background: Endocervical adenocarcinoma (ECA) comprises a heterogeneous group of diseases whose incidence has increased significantly in recent decades. ECA can be histologically classified into human papillomavirus-associated (HPVA) and non-HPVA (NHPVA) types. Given the variability in pathological features and clinical behavior between the subtypes, evaluating their respective immune microenvironments is essential. They can be categorized into distinct tumor microenvironment immune types (TMIT). Methods: A total of 540 surgically resected ECA samples were classified into HPVA and NHPVA subgroups. Tumor-infiltrating immune markers were assessed using immunohistochemistry. We categorized ECA into four TMIT based on PD-L1 and CD8+ tumor-infiltrating lymphocytes (TILs) expression, and analyzed their prognostic significance. Results: PD-L1 positivity was observed in 319 out of 464 (68.8%) HPVA and 55 out of 76 (72.4%) NHPVA. Across the entire cohort, high CD8+ TILs expression was significantly associated with improved disease-free survival (DFS, p=0.018) and overall survival (OS, p=0.031). A total of 177 samples (32.8%) were classified as TMIT I (high PD-L1 and high CD8+ TILs), exhibiting markedly denser immune cell infiltration compared to the other TMIT groups. In NHPVA subgroup, TMIT was significantly associated with both DFS (p=0.005) and OS (p=0.003). Multivariate analysis identified TMIT as an independent prognostic factor for DFS in the NHPVA group, with TMIT I indicating a more favorable prognosis (p=0.042). Conclusions: TMIT I group within the NHPVA population is most likely to benefit from PD-L1/PD-1 blockade immunotherapies. The immune classification of ECA demonstrates significant prognostic value, suggesting its potential utility in guiding clinical stratification and therapeutic decision-making.http://www.sciencedirect.com/science/article/pii/S1936523324003917PD-L1Tumor-infiltrating lymphocytesEndocervical adenocarcinomaPrognosis
spellingShingle Li-Jun Wei
Zi-Yun Wu
Li-Yan Wu
Ying-Wen Wu
Hao-Yu Liang
Rong-Zhen Luo
Li-Li Liu
Prognostic implications of immune classification based on PD-L1 expression and tumor-infiltrating lymphocytes in endocervical adenocarcinoma
Translational Oncology
PD-L1
Tumor-infiltrating lymphocytes
Endocervical adenocarcinoma
Prognosis
title Prognostic implications of immune classification based on PD-L1 expression and tumor-infiltrating lymphocytes in endocervical adenocarcinoma
title_full Prognostic implications of immune classification based on PD-L1 expression and tumor-infiltrating lymphocytes in endocervical adenocarcinoma
title_fullStr Prognostic implications of immune classification based on PD-L1 expression and tumor-infiltrating lymphocytes in endocervical adenocarcinoma
title_full_unstemmed Prognostic implications of immune classification based on PD-L1 expression and tumor-infiltrating lymphocytes in endocervical adenocarcinoma
title_short Prognostic implications of immune classification based on PD-L1 expression and tumor-infiltrating lymphocytes in endocervical adenocarcinoma
title_sort prognostic implications of immune classification based on pd l1 expression and tumor infiltrating lymphocytes in endocervical adenocarcinoma
topic PD-L1
Tumor-infiltrating lymphocytes
Endocervical adenocarcinoma
Prognosis
url http://www.sciencedirect.com/science/article/pii/S1936523324003917
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