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


Journal

Journal for immunotherapy of cancer
ISSN: 2051-1426
Titre abrégé: J Immunother Cancer
Pays: England
ID NLM: 101620585

Informations de publication

Date de publication:
15 Jul 2024
Historique:
accepted: 01 05 2024
medline: 16 7 2024
pubmed: 16 7 2024
entrez: 15 7 2024
Statut: epublish

Résumé

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. 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. 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. 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.

Sections du résumé

BACKGROUND 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 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 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 CONCLUSIONS
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.

Identifiants

pubmed: 39009451
pii: jitc-2023-008734
doi: 10.1136/jitc-2023-008734
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: None declared.

Auteurs

Gaurav Thareja (G)

Weill Cornell Medicine, Doha, Qatar.

Anna Salvioni (A)

Centre de recherche en cancerologie de Toulouse, Toulouse, France.

Françoise Lauzeral-Vizcaino (F)

Centre de Recherches en Cancérologie de Toulouse INSERM UMR1037, Toulouse, France.

Najeeb Halabi (N)

Weill Cornell Medicine, Doha, Qatar.

Eliane Mery-Lamarche (E)

Pathology Department, Oncopole Claudius Regaud, Institut Universitaire du Cancer Toulouse Oncopole, Toulouse, France.

Noemie Thebault (N)

Centre de Recherches en Cancérologie de Toulouse INSERM UMR1037, Toulouse, France.

Clara-Maria Scarlata (CM)

Centre de Recherches en Cancérologie de Toulouse INSERM UMR1037, Toulouse, France.

Marie Michelas (M)

Centre de Recherches en Cancérologie de Toulouse INSERM UMR1037, Toulouse, France.

Anne-Sophie Navarro (AS)

Surgical Oncology Department, Oncopole Claudius Regaud, Institut Universitaire du Cancer Toulouse Oncopole, Toulouse, France.

Gwenaël Ferron (G)

Centre de Recherches en Cancérologie de Toulouse INSERM UMR1037, Toulouse, France.
Surgical Oncology Department, Oncopole Claudius Regaud, Institut Universitaire du Cancer Toulouse Oncopole, Toulouse, France.

Fabrice Lecuru (F)

Gynecologic Oncology Department, Institut Curie, Paris, France.
Paris Cité University, Paris, France.

Patrice Mathevet (P)

Gynecology Department, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

Jonathan Khalifa (J)

Centre de Recherches en Cancérologie de Toulouse INSERM UMR1037, Toulouse, France.
Radiotherapy Department, Oncopole Claudius Regaud, Institut Universitaire du Cancer Toulouse Oncopole, Toulouse, France.

Maha Ayyoub (M)

Centre de Recherches en Cancérologie de Toulouse INSERM UMR1037, Toulouse, France.

Arash Rafii (A)

ScieNFT, Paris, France.

Alejandra Martinez (A)

Centre de Recherches en Cancérologie de Toulouse INSERM UMR1037, Toulouse, France martinez.alejandra@iuct-oncopole.fr.
Surgical Oncology Department, Oncopole Claudius Regaud, Institut Universitaire du Cancer Toulouse Oncopole, Toulouse, France.
Toulouse III-Paul Sabatier University, Toulouse, France.

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Classifications MeSH