Liver metastases of colorectal cancer contain different subsets of tissue-resident memory CD8 T cells correlated with a distinct risk of relapse following surgery

Tissue-resident memory (TRM) T cells have emerged as key players in cancer immunosurveillance, and their presence has been linked to a favorable clinical outcome in solid cancer patients. Liver metastases exhibit a highly immunosuppressive tumor microenvironment, however, the role and clinical impac...

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Main Authors: Syrine Abdeljaoued, Alexandre Doussot, Marie Kroemer, Emilien Laloy, Jean René Pallandre, Antoine El Kaddissi, Laurie Spehner, Myriam Ben Khelil, Adeline Bouard, Virginie Mougey, Ugo Chartral, Angélique Vienot, Julien Viot, Zaher Lakkis, Franck Monnien, Romain Loyon, Christophe Borg
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:OncoImmunology
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Online Access:https://www.tandfonline.com/doi/10.1080/2162402X.2025.2455176
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author Syrine Abdeljaoued
Alexandre Doussot
Marie Kroemer
Emilien Laloy
Jean René Pallandre
Antoine El Kaddissi
Laurie Spehner
Myriam Ben Khelil
Adeline Bouard
Virginie Mougey
Ugo Chartral
Angélique Vienot
Julien Viot
Zaher Lakkis
Franck Monnien
Romain Loyon
Christophe Borg
author_facet Syrine Abdeljaoued
Alexandre Doussot
Marie Kroemer
Emilien Laloy
Jean René Pallandre
Antoine El Kaddissi
Laurie Spehner
Myriam Ben Khelil
Adeline Bouard
Virginie Mougey
Ugo Chartral
Angélique Vienot
Julien Viot
Zaher Lakkis
Franck Monnien
Romain Loyon
Christophe Borg
author_sort Syrine Abdeljaoued
collection DOAJ
description Tissue-resident memory (TRM) T cells have emerged as key players in cancer immunosurveillance, and their presence has been linked to a favorable clinical outcome in solid cancer patients. Liver metastases exhibit a highly immunosuppressive tumor microenvironment, however, the role and clinical impact of TRM cell infiltration in colorectal cancer remain elusive. The expression of several tissue residency and activation biomarkers has been investigated on tumor-infiltrating lymphocytes isolated from 26 patients’ colorectal cancer liver metastases (CRC liver metastases) and compared to 16 peripheral blood samples of patients with CRC liver metastases. Cytokine production was also evaluated in in vitro-activated TRM and non-TRM cells. The prognostic value of TRM cells was also assessed in a well-defined cohort of CRC liver metastases. Here we identified two subsets of TRM cells expressing CD103 and/or CD69 showing significantly higher expression of tissue residency and activation biomarkers. CD103+CD69+ TRM cells subset showed almost exclusive expression of tumor reactivity biomarkers PD-1 and CD39. Supporting this observation, CD103+CD69+ TRM cells showed a more oligoclonal TCR repertoire. Both TRM subsets presented higher cytotoxic and functional capacity compared to non-TRM cells. Our study shows that only the presence of CD103+CD69+ TRM cells is associated with longer recurrence-free survival of colorectal cancer patients with liver metastases. Taken together, our work demonstrates the existence of a phenotypic heterogeneity of TRM cells in colorectal cancer liver metastases. In this study, we identified a population of CD103+CD69+ TRM cells exhibiting the characteristics of tumor reactivity and correlated with better patients’ prognosis, with potential implications in optimal therapeutic strategies determination.
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spelling doaj-art-09ee3f0e36ba493bbe6b5d913534653d2025-01-23T08:01:55ZengTaylor & Francis GroupOncoImmunology2162-402X2025-12-0114110.1080/2162402X.2025.2455176Liver metastases of colorectal cancer contain different subsets of tissue-resident memory CD8 T cells correlated with a distinct risk of relapse following surgerySyrine Abdeljaoued0Alexandre Doussot1Marie Kroemer2Emilien Laloy3Jean René Pallandre4Antoine El Kaddissi5Laurie Spehner6Myriam Ben Khelil7Adeline Bouard8Virginie Mougey9Ugo Chartral10Angélique Vienot11Julien Viot12Zaher Lakkis13Franck Monnien14Romain Loyon15Christophe Borg16Université de Franche-Comté, EFS, INSERM, UMR RIGHT, Besançon, FranceDepartment of Digestive and Oncologic Surgery, Liver Transplantation Unit, University Hospital of Besançon, Besançon, FranceUniversité de Franche-Comté, EFS, INSERM, UMR RIGHT, Besançon, FranceUniversité de Franche-Comté, EFS, INSERM, UMR RIGHT, Besançon, FranceUniversité de Franche-Comté, EFS, INSERM, UMR RIGHT, Besançon, FranceUniversité de Franche-Comté, EFS, INSERM, UMR RIGHT, Besançon, FranceUniversité de Franche-Comté, EFS, INSERM, UMR RIGHT, Besançon, FranceUniversité de Franche-Comté, EFS, INSERM, UMR RIGHT, Besançon, FranceUniversité de Franche-Comté, EFS, INSERM, UMR RIGHT, Besançon, FranceUniversité de Franche-Comté, EFS, INSERM, UMR RIGHT, Besançon, FranceUniversité de Franche-Comté, EFS, INSERM, UMR RIGHT, Besançon, FranceUniversité de Franche-Comté, EFS, INSERM, UMR RIGHT, Besançon, FranceUniversité de Franche-Comté, EFS, INSERM, UMR RIGHT, Besançon, FranceUniversité de Franche-Comté, EFS, INSERM, UMR RIGHT, Besançon, FranceUniversité de Franche-Comté, EFS, INSERM, UMR RIGHT, Besançon, FranceUniversité de Franche-Comté, EFS, INSERM, UMR RIGHT, Besançon, FranceUniversité de Franche-Comté, EFS, INSERM, UMR RIGHT, Besançon, FranceTissue-resident memory (TRM) T cells have emerged as key players in cancer immunosurveillance, and their presence has been linked to a favorable clinical outcome in solid cancer patients. Liver metastases exhibit a highly immunosuppressive tumor microenvironment, however, the role and clinical impact of TRM cell infiltration in colorectal cancer remain elusive. The expression of several tissue residency and activation biomarkers has been investigated on tumor-infiltrating lymphocytes isolated from 26 patients’ colorectal cancer liver metastases (CRC liver metastases) and compared to 16 peripheral blood samples of patients with CRC liver metastases. Cytokine production was also evaluated in in vitro-activated TRM and non-TRM cells. The prognostic value of TRM cells was also assessed in a well-defined cohort of CRC liver metastases. Here we identified two subsets of TRM cells expressing CD103 and/or CD69 showing significantly higher expression of tissue residency and activation biomarkers. CD103+CD69+ TRM cells subset showed almost exclusive expression of tumor reactivity biomarkers PD-1 and CD39. Supporting this observation, CD103+CD69+ TRM cells showed a more oligoclonal TCR repertoire. Both TRM subsets presented higher cytotoxic and functional capacity compared to non-TRM cells. Our study shows that only the presence of CD103+CD69+ TRM cells is associated with longer recurrence-free survival of colorectal cancer patients with liver metastases. Taken together, our work demonstrates the existence of a phenotypic heterogeneity of TRM cells in colorectal cancer liver metastases. In this study, we identified a population of CD103+CD69+ TRM cells exhibiting the characteristics of tumor reactivity and correlated with better patients’ prognosis, with potential implications in optimal therapeutic strategies determination.https://www.tandfonline.com/doi/10.1080/2162402X.2025.2455176Colorectal cancerliver metastasesprognosisTissue-resident memory t cellsTRM
spellingShingle Syrine Abdeljaoued
Alexandre Doussot
Marie Kroemer
Emilien Laloy
Jean René Pallandre
Antoine El Kaddissi
Laurie Spehner
Myriam Ben Khelil
Adeline Bouard
Virginie Mougey
Ugo Chartral
Angélique Vienot
Julien Viot
Zaher Lakkis
Franck Monnien
Romain Loyon
Christophe Borg
Liver metastases of colorectal cancer contain different subsets of tissue-resident memory CD8 T cells correlated with a distinct risk of relapse following surgery
OncoImmunology
Colorectal cancer
liver metastases
prognosis
Tissue-resident memory t cells
TRM
title Liver metastases of colorectal cancer contain different subsets of tissue-resident memory CD8 T cells correlated with a distinct risk of relapse following surgery
title_full Liver metastases of colorectal cancer contain different subsets of tissue-resident memory CD8 T cells correlated with a distinct risk of relapse following surgery
title_fullStr Liver metastases of colorectal cancer contain different subsets of tissue-resident memory CD8 T cells correlated with a distinct risk of relapse following surgery
title_full_unstemmed Liver metastases of colorectal cancer contain different subsets of tissue-resident memory CD8 T cells correlated with a distinct risk of relapse following surgery
title_short Liver metastases of colorectal cancer contain different subsets of tissue-resident memory CD8 T cells correlated with a distinct risk of relapse following surgery
title_sort liver metastases of colorectal cancer contain different subsets of tissue resident memory cd8 t cells correlated with a distinct risk of relapse following surgery
topic Colorectal cancer
liver metastases
prognosis
Tissue-resident memory t cells
TRM
url https://www.tandfonline.com/doi/10.1080/2162402X.2025.2455176
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