A Tertiary lymphoid structures-based pathological score predicts survival and recurrence in colorectal Cancer patients

Background & Aim: Colorectal cancer (CRC) is a major global health burden. The immune response within the tumor microenvironment (TME), especially the presence of tertiary lymphoid structures (TLS), plays a critical role in prognosis. However, current prognostic tools often overlook this imm...

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Main Authors: Marion Le Rochais, Marie Morvan, Servane Bouzeloc, Jean-Baptiste Nousbaum, Matthieu Guillard, Pierre Le Noac'h, Soizic Garaud, Arnaud Uguen
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:Immunobiology
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Online Access:http://www.sciencedirect.com/science/article/pii/S0171298525000452
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author Marion Le Rochais
Marie Morvan
Servane Bouzeloc
Jean-Baptiste Nousbaum
Matthieu Guillard
Pierre Le Noac'h
Soizic Garaud
Arnaud Uguen
author_facet Marion Le Rochais
Marie Morvan
Servane Bouzeloc
Jean-Baptiste Nousbaum
Matthieu Guillard
Pierre Le Noac'h
Soizic Garaud
Arnaud Uguen
author_sort Marion Le Rochais
collection DOAJ
description Background &amp; Aim: Colorectal cancer (CRC) is a major global health burden. The immune response within the tumor microenvironment (TME), especially the presence of tertiary lymphoid structures (TLS), plays a critical role in prognosis. However, current prognostic tools often overlook this immune component. This study aimed to characterize TLS in CRC and develop a TLS-score correlating with survival outcomes. Methods: We conducted a retrospective analysis of 7895 TLS from 806 CRC patients using data from the Finistere Registry of Digestive Tumors. Hematoxylin-eosin-saffron (HES) staining and immunohistochemistry (IHC) were employed for TLS quantification to explore their relationship with survival and recurrence metrics. Results: Patients with microsatellite instability (MSI) demonstrated higher TLS density and more mature TLS. Both TLS density and maturation showed significant correlations with overall survival (OS) and disease-free survival (DFS). Kaplan-Meier analysis revealed that increased TLS density and GC-like maturation correlated with improved OS and DFS. Our novel pathological TLS score, integrating density and maturation, effectively stratified patients by survival and recurrence risk, distinguishing high-risk individuals (score 0–1–2) with poorer outcomes from low-risk patients (score 3–4) with better prognosis (p < 0.0001), particularly in stage II–III cases. Conclusion: TLS density and maturation are robust prognostic markers in CRC. The proposed TLS score may aid pathologists in identifying patients at higher recurrence risk and poorer survival, guiding clinical decisions for monitoring and potential adjuvant therapies. Further validation of these findings is essential before clinical implementation.
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spelling doaj-art-c94d3fdd33e24d8897e34f1d521531862025-08-20T02:03:14ZengElsevierImmunobiology0171-29852025-05-01230315291110.1016/j.imbio.2025.152911A Tertiary lymphoid structures-based pathological score predicts survival and recurrence in colorectal Cancer patientsMarion Le Rochais0Marie Morvan1Servane Bouzeloc2Jean-Baptiste Nousbaum3Matthieu Guillard4Pierre Le Noac'h5Soizic Garaud6Arnaud Uguen7LBAI, UMR1227, Univ Brest, Inserm, Brest, France,; Corresponding author: B Lymphocytes, Autoimmunity and Immunotherapies - UMR1227; Immunology Department - Augustin Morvan Hospital, Brest 29200, France.Registre des Tumeurs Digestives du Finistère, Brest, France; EA7479 SPURBO, Université de Bretagne Occidentale, Brest, FranceRegistre des Tumeurs Digestives du Finistère, Brest, France; EA7479 SPURBO, Université de Bretagne Occidentale, Brest, FranceRegistre des Tumeurs Digestives du Finistère, Brest, France; CHU Brest, Hepato-gastroenterology Department, Brest, France; EA7479 SPURBO, Université de Bretagne Occidentale, Brest, FranceCHU Brest, Pathology Department, Brest, FranceCHU Brest, Oncology Department, Brest, FranceLBAI, UMR1227, Univ Brest, Inserm, Brest, France,LBAI, UMR1227, Univ Brest, Inserm, Brest, France,; CHU Brest, Pathology Department, Brest, FranceBackground &amp; Aim: Colorectal cancer (CRC) is a major global health burden. The immune response within the tumor microenvironment (TME), especially the presence of tertiary lymphoid structures (TLS), plays a critical role in prognosis. However, current prognostic tools often overlook this immune component. This study aimed to characterize TLS in CRC and develop a TLS-score correlating with survival outcomes. Methods: We conducted a retrospective analysis of 7895 TLS from 806 CRC patients using data from the Finistere Registry of Digestive Tumors. Hematoxylin-eosin-saffron (HES) staining and immunohistochemistry (IHC) were employed for TLS quantification to explore their relationship with survival and recurrence metrics. Results: Patients with microsatellite instability (MSI) demonstrated higher TLS density and more mature TLS. Both TLS density and maturation showed significant correlations with overall survival (OS) and disease-free survival (DFS). Kaplan-Meier analysis revealed that increased TLS density and GC-like maturation correlated with improved OS and DFS. Our novel pathological TLS score, integrating density and maturation, effectively stratified patients by survival and recurrence risk, distinguishing high-risk individuals (score 0–1–2) with poorer outcomes from low-risk patients (score 3–4) with better prognosis (p < 0.0001), particularly in stage II–III cases. Conclusion: TLS density and maturation are robust prognostic markers in CRC. The proposed TLS score may aid pathologists in identifying patients at higher recurrence risk and poorer survival, guiding clinical decisions for monitoring and potential adjuvant therapies. Further validation of these findings is essential before clinical implementation.http://www.sciencedirect.com/science/article/pii/S0171298525000452Colorectal cancerTertiary lymphoid structuresPrognosisDigital pathology
spellingShingle Marion Le Rochais
Marie Morvan
Servane Bouzeloc
Jean-Baptiste Nousbaum
Matthieu Guillard
Pierre Le Noac'h
Soizic Garaud
Arnaud Uguen
A Tertiary lymphoid structures-based pathological score predicts survival and recurrence in colorectal Cancer patients
Immunobiology
Colorectal cancer
Tertiary lymphoid structures
Prognosis
Digital pathology
title A Tertiary lymphoid structures-based pathological score predicts survival and recurrence in colorectal Cancer patients
title_full A Tertiary lymphoid structures-based pathological score predicts survival and recurrence in colorectal Cancer patients
title_fullStr A Tertiary lymphoid structures-based pathological score predicts survival and recurrence in colorectal Cancer patients
title_full_unstemmed A Tertiary lymphoid structures-based pathological score predicts survival and recurrence in colorectal Cancer patients
title_short A Tertiary lymphoid structures-based pathological score predicts survival and recurrence in colorectal Cancer patients
title_sort tertiary lymphoid structures based pathological score predicts survival and recurrence in colorectal cancer patients
topic Colorectal cancer
Tertiary lymphoid structures
Prognosis
Digital pathology
url http://www.sciencedirect.com/science/article/pii/S0171298525000452
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