Location matters: spatial dynamics of tumor-infiltrating T cell subsets is prognostic in colon cancer.

T cell colon cancer immunologic constant of rejection multiplex immunofluorescence spatial analysis tumor microenvironment

Journal

Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960

Informations de publication

Date de publication:
2024
Historique:
received: 13 09 2023
accepted: 16 01 2024
medline: 20 2 2024
pubmed: 20 2 2024
entrez: 20 2 2024
Statut: epublish

Résumé

Colon cancer is a heterogeneous disease and consists of various molecular subtypes. Despite advances in high-throughput expression profiling, limitations remain in predicting clinical outcome and assigning specific treatment to individual cases. Tumor-immune interactions play a critical role, with tumors that activate the immune system having better outcome for the patient. The localization of T cells within tumor epithelium, to enable direct contact, is essential for antitumor function, but bulk DNA/RNA sequencing data lacks spatial distribution information. In this study, we provide spatial T cell tumor distribution and connect these data with previously determined genomic data in the AC-ICAM colon cancer patient cohort. Colon cancer patients (n=90) with transcriptome data available were selected. We used a custom multiplex immunofluorescence assay on colon tumor tissue sections for quantifying T cell subsets spatial distribution in the tumor microenvironment, in terms of cell number, location, mutual distance, and distance to tumor cells. Statistical analyses included the previously determined Immunologic Constant of Rejection (ICR) transcriptome correlation and patient survival, revealing potential prognostic value in T cell spatial distribution. T cell phenotypes were characterized and CD3 Our study's in-depth analysis of the spatial distribution and densities of major T cell subtypes within the tumor microenvironment has provided valuable information that paves the way for further research into the intricate relationships between immune cells and colon cancer development.

Sections du résumé

Background UNASSIGNED
Colon cancer is a heterogeneous disease and consists of various molecular subtypes. Despite advances in high-throughput expression profiling, limitations remain in predicting clinical outcome and assigning specific treatment to individual cases. Tumor-immune interactions play a critical role, with tumors that activate the immune system having better outcome for the patient. The localization of T cells within tumor epithelium, to enable direct contact, is essential for antitumor function, but bulk DNA/RNA sequencing data lacks spatial distribution information. In this study, we provide spatial T cell tumor distribution and connect these data with previously determined genomic data in the AC-ICAM colon cancer patient cohort.
Methods UNASSIGNED
Colon cancer patients (n=90) with transcriptome data available were selected. We used a custom multiplex immunofluorescence assay on colon tumor tissue sections for quantifying T cell subsets spatial distribution in the tumor microenvironment, in terms of cell number, location, mutual distance, and distance to tumor cells. Statistical analyses included the previously determined Immunologic Constant of Rejection (ICR) transcriptome correlation and patient survival, revealing potential prognostic value in T cell spatial distribution.
Results UNASSIGNED
T cell phenotypes were characterized and CD3
Conclusion UNASSIGNED
Our study's in-depth analysis of the spatial distribution and densities of major T cell subtypes within the tumor microenvironment has provided valuable information that paves the way for further research into the intricate relationships between immune cells and colon cancer development.

Identifiants

pubmed: 38375478
doi: 10.3389/fimmu.2024.1293618
pmc: PMC10875018
doi:

Banques de données

figshare
['10.6084/m9.figshare.16944775']

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1293618

Informations de copyright

Copyright © 2024 Zhu, Roelands, Ahmed, Stouten, Hoorntje, van Vlierberghe, Ijsselsteijn, Lei, de Miranda, Tollenaar, Vahrmeijer, Bedognetti, Hendrickx and Kuppen.

Déclaration de conflit d'intérêts

DB reports employment with Kite, a Gilead Company. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Auteurs

Hehuan Zhu (H)

Department of Surgery, Leiden University Medical Center, Leiden, Netherlands.

Jessica Roelands (J)

Department of Surgery, Leiden University Medical Center, Leiden, Netherlands.
Department of Pathology, Leiden University Medical Center, Leiden, Netherlands.
Translational Medicine Division, Research Branch, Sidra Medicine, Doha, Qatar.

Eiman I Ahmed (EI)

Translational Medicine Division, Research Branch, Sidra Medicine, Doha, Qatar.
Department of Biomedical Science, College of Health Sciences, Qatar University, Doha, Qatar.
College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar.

Imke Stouten (I)

Department of Surgery, Leiden University Medical Center, Leiden, Netherlands.

Rachel Hoorntje (R)

Department of Surgery, Leiden University Medical Center, Leiden, Netherlands.

Ronald L P van Vlierberghe (RLP)

Department of Surgery, Leiden University Medical Center, Leiden, Netherlands.

Marieke E Ijsselsteijn (ME)

Department of Pathology, Leiden University Medical Center, Leiden, Netherlands.

Xin Lei (X)

Department of Immunology and Oncode Institute, Leiden University Medical Center, Leiden, Netherlands.

Noel F C C de Miranda (NFCC)

Department of Pathology, Leiden University Medical Center, Leiden, Netherlands.

Rob A E M Tollenaar (RAEM)

Department of Surgery, Leiden University Medical Center, Leiden, Netherlands.

Alexander L Vahrmeijer (AL)

Department of Surgery, Leiden University Medical Center, Leiden, Netherlands.

Davide Bedognetti (D)

College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar.
Kite, A Gilead Company, Santa Monica, CA, United States.

Wouter R L Hendrickx (WRL)

College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar.
Tumor Biology and Immunology Lab, Research Branch, Sidra Medicine, Doha, Qatar.

Peter J K Kuppen (PJK)

Department of Surgery, Leiden University Medical Center, Leiden, Netherlands.

Classifications MeSH