Assessing the implications of sentinel lymph node removal in cervical cancer: an immunogenetic perspective – a SENTICOL ancillary study

Background Cervical cancer’s lymphatic spread primarily begins from the sentinel lymph nodes (SLNs), underlining their pivotal role in disease metastasis. However, these nodes’ immune gene expression profiles and immunoregulation mechanisms have yet to be explored.Methods Our study aimed to elucidat...

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Main Authors: Alejandra Martinez, Gwenael Ferron, Fabrice Lécuru, Patrice Mathevet, Maha Ayyoub, Anne-Sophie Navarro, Arash Rafii, Anna Salvioni, Marie Michelas, Gaurav Thareja, Françoise Lauzeral-Vizcaino, Najeeb Halabi, Eliane Mery-Lamarche, Noemie Thebault, Clara-Maria Scarlata, Jonathan Khalifa
Format: Article
Language:English
Published: BMJ Publishing Group 2024-07-01
Series:Journal for ImmunoTherapy of Cancer
Online Access:https://jitc.bmj.com/content/12/7/e008734.full
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author Alejandra Martinez
Gwenael Ferron
Fabrice Lécuru
Patrice Mathevet
Maha Ayyoub
Anne-Sophie Navarro
Arash Rafii
Anna Salvioni
Marie Michelas
Gaurav Thareja
Françoise Lauzeral-Vizcaino
Najeeb Halabi
Eliane Mery-Lamarche
Noemie Thebault
Clara-Maria Scarlata
Jonathan Khalifa
author_facet Alejandra Martinez
Gwenael Ferron
Fabrice Lécuru
Patrice Mathevet
Maha Ayyoub
Anne-Sophie Navarro
Arash Rafii
Anna Salvioni
Marie Michelas
Gaurav Thareja
Françoise Lauzeral-Vizcaino
Najeeb Halabi
Eliane Mery-Lamarche
Noemie Thebault
Clara-Maria Scarlata
Jonathan Khalifa
author_sort Alejandra Martinez
collection DOAJ
description Background Cervical cancer’s lymphatic spread primarily begins from the sentinel lymph nodes (SLNs), underlining their pivotal role in disease metastasis. However, these nodes’ immune gene expression profiles and immunoregulation mechanisms have yet to be explored.Methods Our study aimed to elucidate the immune cell populations and their roles in the immune gene expression profile of negative SLNs compared with positive SLNs and non-SLNs using Nanostring RNA seq analysis. We performed a principal component analysis on the log2 normalized expression of 685 endogenous genes in the nCounter PanCancer Immune Profiling Panel, followed by an assessment of the differential expression of genes and immune cell type abundance.Results We found significant variations in gene expression among the groups, with negative SLNs displaying overexpression of genes related to tumor-infiltrating immune cells, specifically innate cell populations. They also demonstrated the upregulation of genes involved in antigen presentation and T-cell priming. In contrast, positive SLNs were enriched in regulatory networks, suggesting their potential role in immune evasion. A comparison of negative SLNs and non-SLNs revealed increased innate and adaptive immune cell types, underscoring the ongoing T cell response to tumor antigens.Conclusion Our findings underscore a specific immunogenetic phenotype profile in negative SLNs, emphasizing their crucial role in the initial anticancer response, immunosurveillance, and the propagation of immune tolerance from the primary cervical tumor. These results highlight the potential of SLNs as a novel target for immunotherapy strategies and underscore the importance of new imaging methods for accurately identifying SLN status without removal. Future investigations are needed to understand further the immunological interplay within SLNs and their influence on cervical cancer progression.
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spelling doaj-art-8be0f11ddce545bb8838776ab4c78f1f2025-08-20T03:16:24ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262024-07-0112710.1136/jitc-2023-008734Assessing the implications of sentinel lymph node removal in cervical cancer: an immunogenetic perspective – a SENTICOL ancillary studyAlejandra Martinez0Gwenael Ferron1Fabrice Lécuru2Patrice Mathevet3Maha Ayyoub4Anne-Sophie Navarro5Arash Rafii6Anna Salvioni7Marie Michelas8Gaurav Thareja9Françoise Lauzeral-Vizcaino10Najeeb Halabi11Eliane Mery-Lamarche12Noemie Thebault13Clara-Maria Scarlata14Jonathan Khalifa154 Department of Surgical Oncology, Institut Universitaire du Cancer Toulouse Oncopole, Toulouse, France1Department of Surgical Oncology, Institut Universitaire du Cancer de Toulouse – Oncopole, Toulouse, FranceParis Cité University, Paris, France20 Centre Hospitalier Universitaire Vaudois Departement de gynecologie-obstetrique et genetique medicale, Lausanne, SwitzerlandCentre de Recherches en Cancérologie de Toulouse INSERM UMR1037, Toulouse, FranceDepartment of Surgical Oncology, Institut Universitaire du Cancer Toulouse Oncopole Departement de chirurgie, Toulouse, Languedoc-Roussillon Midi, FranceScieNFT, Paris, FranceCentre de recherche en cancerologie de Toulouse, Toulouse, FranceCentre de Recherches en Cancérologie de Toulouse INSERM UMR1037, Toulouse, FranceWeill Cornell Medicine, Doha, QatarCentre de Recherches en Cancérologie de Toulouse INSERM UMR1037, Toulouse, FranceWeill Cornell Medicine, Doha, QatarPathology Department, Oncopole Claudius Regaud, Institut Universitaire du Cancer Toulouse Oncopole, Toulouse, FranceCentre de Recherches en Cancérologie de Toulouse INSERM UMR1037, Toulouse, FranceCentre de Recherches en Cancérologie de Toulouse INSERM UMR1037, Toulouse, FranceCentre de Recherches en Cancérologie de Toulouse INSERM UMR1037, Toulouse, FranceBackground Cervical cancer’s lymphatic spread primarily begins from the sentinel lymph nodes (SLNs), underlining their pivotal role in disease metastasis. However, these nodes’ immune gene expression profiles and immunoregulation mechanisms have yet to be explored.Methods Our study aimed to elucidate the immune cell populations and their roles in the immune gene expression profile of negative SLNs compared with positive SLNs and non-SLNs using Nanostring RNA seq analysis. We performed a principal component analysis on the log2 normalized expression of 685 endogenous genes in the nCounter PanCancer Immune Profiling Panel, followed by an assessment of the differential expression of genes and immune cell type abundance.Results We found significant variations in gene expression among the groups, with negative SLNs displaying overexpression of genes related to tumor-infiltrating immune cells, specifically innate cell populations. They also demonstrated the upregulation of genes involved in antigen presentation and T-cell priming. In contrast, positive SLNs were enriched in regulatory networks, suggesting their potential role in immune evasion. A comparison of negative SLNs and non-SLNs revealed increased innate and adaptive immune cell types, underscoring the ongoing T cell response to tumor antigens.Conclusion Our findings underscore a specific immunogenetic phenotype profile in negative SLNs, emphasizing their crucial role in the initial anticancer response, immunosurveillance, and the propagation of immune tolerance from the primary cervical tumor. These results highlight the potential of SLNs as a novel target for immunotherapy strategies and underscore the importance of new imaging methods for accurately identifying SLN status without removal. Future investigations are needed to understand further the immunological interplay within SLNs and their influence on cervical cancer progression.https://jitc.bmj.com/content/12/7/e008734.full
spellingShingle Alejandra Martinez
Gwenael Ferron
Fabrice Lécuru
Patrice Mathevet
Maha Ayyoub
Anne-Sophie Navarro
Arash Rafii
Anna Salvioni
Marie Michelas
Gaurav Thareja
Françoise Lauzeral-Vizcaino
Najeeb Halabi
Eliane Mery-Lamarche
Noemie Thebault
Clara-Maria Scarlata
Jonathan Khalifa
Assessing the implications of sentinel lymph node removal in cervical cancer: an immunogenetic perspective – a SENTICOL ancillary study
Journal for ImmunoTherapy of Cancer
title Assessing the implications of sentinel lymph node removal in cervical cancer: an immunogenetic perspective – a SENTICOL ancillary study
title_full Assessing the implications of sentinel lymph node removal in cervical cancer: an immunogenetic perspective – a SENTICOL ancillary study
title_fullStr Assessing the implications of sentinel lymph node removal in cervical cancer: an immunogenetic perspective – a SENTICOL ancillary study
title_full_unstemmed Assessing the implications of sentinel lymph node removal in cervical cancer: an immunogenetic perspective – a SENTICOL ancillary study
title_short Assessing the implications of sentinel lymph node removal in cervical cancer: an immunogenetic perspective – a SENTICOL ancillary study
title_sort assessing the implications of sentinel lymph node removal in cervical cancer an immunogenetic perspective a senticol ancillary study
url https://jitc.bmj.com/content/12/7/e008734.full
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