The single-cell spatial landscape of stage III colorectal cancers

Abstract We conducted a spatial analysis of stage III colorectal adenocarcinomas using Hyperion Imaging Mass Cytometry, examining 52 tumors to assess the tumor microenvironment at the single-cell level. This approach identified 10 distinct cell phenotypes in the tumor microenvironment, including str...

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Main Authors: Andrew Su, HoJoon Lee, Minh Tran, Richard C. dela Cruz, Anuja Sathe, Xiangqi Bai, Ignacio Wichmann, Lance Pflieger, Bryce Moulton, Tyler Barker, Derrick Haslem, David Jones, Lincoln Nadauld, Quan Nguyen, Hanlee P. Ji, Terence Rhodes
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:npj Precision Oncology
Online Access:https://doi.org/10.1038/s41698-025-00853-5
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author Andrew Su
HoJoon Lee
Minh Tran
Richard C. dela Cruz
Anuja Sathe
Xiangqi Bai
Ignacio Wichmann
Lance Pflieger
Bryce Moulton
Tyler Barker
Derrick Haslem
David Jones
Lincoln Nadauld
Quan Nguyen
Hanlee P. Ji
Terence Rhodes
author_facet Andrew Su
HoJoon Lee
Minh Tran
Richard C. dela Cruz
Anuja Sathe
Xiangqi Bai
Ignacio Wichmann
Lance Pflieger
Bryce Moulton
Tyler Barker
Derrick Haslem
David Jones
Lincoln Nadauld
Quan Nguyen
Hanlee P. Ji
Terence Rhodes
author_sort Andrew Su
collection DOAJ
description Abstract We conducted a spatial analysis of stage III colorectal adenocarcinomas using Hyperion Imaging Mass Cytometry, examining 52 tumors to assess the tumor microenvironment at the single-cell level. This approach identified 10 distinct cell phenotypes in the tumor microenvironment, including stromal and immune cells, with a subset showing a proliferative phenotype. By focusing on spatial neighborhood interactions and tissue niches, particularly regions with tumor-infiltrating lymphocytes, we investigated how cellular organization relates to clinicopathological and molecular features such as microsatellite instability (MSI) and recurrence. We determined that microsatellite stable (MSS) colorectal cancers had an increased risk of recurrence if they had the following features: 1) a low level of stromal tumor-infiltrating lymphocytes, and 2) low interactions between CD4 + T cells and stromal cells. Our results point to the utility of spatial single-cell interaction analysis in defining novel features of the tumor immune microenvironments and providing useful clinical cell-related spatial biomarkers.
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series npj Precision Oncology
spelling doaj-art-b824288491bd45a0bdeaebd825021e9a2025-08-20T03:10:09ZengNature Portfolionpj Precision Oncology2397-768X2025-04-019111310.1038/s41698-025-00853-5The single-cell spatial landscape of stage III colorectal cancersAndrew Su0HoJoon Lee1Minh Tran2Richard C. dela Cruz3Anuja Sathe4Xiangqi Bai5Ignacio Wichmann6Lance Pflieger7Bryce Moulton8Tyler Barker9Derrick Haslem10David Jones11Lincoln Nadauld12Quan Nguyen13Hanlee P. Ji14Terence Rhodes15Division of Oncology, Department of Medicine, Stanford University School of MedicineDivision of Oncology, Department of Medicine, Stanford University School of MedicineInstitute for Molecular Bioscience, The University of QueenslandIntermountain HealthcareDivision of Oncology, Department of Medicine, Stanford University School of MedicineDivision of Oncology, Department of Medicine, Stanford University School of MedicineDivision of Oncology, Department of Medicine, Stanford University School of MedicineIntermountain HealthcareIntermountain HealthcareIntermountain HealthcareIntermountain HealthcareIntermountain HealthcareIntermountain HealthcareInstitute for Molecular Bioscience, The University of QueenslandDivision of Oncology, Department of Medicine, Stanford University School of MedicineIntermountain HealthcareAbstract We conducted a spatial analysis of stage III colorectal adenocarcinomas using Hyperion Imaging Mass Cytometry, examining 52 tumors to assess the tumor microenvironment at the single-cell level. This approach identified 10 distinct cell phenotypes in the tumor microenvironment, including stromal and immune cells, with a subset showing a proliferative phenotype. By focusing on spatial neighborhood interactions and tissue niches, particularly regions with tumor-infiltrating lymphocytes, we investigated how cellular organization relates to clinicopathological and molecular features such as microsatellite instability (MSI) and recurrence. We determined that microsatellite stable (MSS) colorectal cancers had an increased risk of recurrence if they had the following features: 1) a low level of stromal tumor-infiltrating lymphocytes, and 2) low interactions between CD4 + T cells and stromal cells. Our results point to the utility of spatial single-cell interaction analysis in defining novel features of the tumor immune microenvironments and providing useful clinical cell-related spatial biomarkers.https://doi.org/10.1038/s41698-025-00853-5
spellingShingle Andrew Su
HoJoon Lee
Minh Tran
Richard C. dela Cruz
Anuja Sathe
Xiangqi Bai
Ignacio Wichmann
Lance Pflieger
Bryce Moulton
Tyler Barker
Derrick Haslem
David Jones
Lincoln Nadauld
Quan Nguyen
Hanlee P. Ji
Terence Rhodes
The single-cell spatial landscape of stage III colorectal cancers
npj Precision Oncology
title The single-cell spatial landscape of stage III colorectal cancers
title_full The single-cell spatial landscape of stage III colorectal cancers
title_fullStr The single-cell spatial landscape of stage III colorectal cancers
title_full_unstemmed The single-cell spatial landscape of stage III colorectal cancers
title_short The single-cell spatial landscape of stage III colorectal cancers
title_sort single cell spatial landscape of stage iii colorectal cancers
url https://doi.org/10.1038/s41698-025-00853-5
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