EP923 - Multiomic phenotyping of tumor-associated macrophages reflects biology and predicts cancer-specific survival in CRC

Monday, May 11, 2026

1:41 PM - 1:46 PM ET

ePoster Presenter(s)

NG

Norman J. Galbraith, MBChB PhD FRCS

Clinical Senior Research Fellow / Consultant Colorectal Surgeon
University of Glasgow / Glasgow Royal Infirmary
Glasgow, Scotland, United Kingdom

Disclosure information not submitted.

Author(s)

AP

Anh Phuong, MRes

PhD student
University of Glasgow
Glasgow, Scotland, United Kingdom

Disclosure information not submitted.
LM

Luke McNickel, MBChB MRCS

Clinical Research Fellow
University of Glasgow
Glasgow, Scotland, United Kingdom

Disclosure information not submitted.
PH

Phimmada Hatthakarnkul, PhD

Post-doc
University of Glasgow
Glasgow, Scotland, United Kingdom

Disclosure information not submitted.
MM

Molly McKenzie, MSc

PhD student
University of Glasgow
Glasgow, Scotland, United Kingdom

Disclosure information not submitted.
AL

Assya Legrini, PhD

Post doc
University of Glasgow
Glasgow, Scotland, United Kingdom

Disclosure information not submitted.
CS

Colin W. Steele, PhD FRCS

Consultant Surgeon & Clinical Senior Lecturer
University of Glasgow
Glasgow, Scotland, United Kingdom

Disclosure information not submitted.
NJ

Nigel Jamieson, MBChB PhD FRCS

Professor of Surgery
University of Glasgow
Glasgow, Scotland, United Kingdom

Disclosure information not submitted.
Campbell S. Roxburgh, PhD (he/him/his)

Professor of Colorectal Surgical Oncology
University of Glasgow
University of Glasgow
Glasgow, Scotland, United Kingdom

Disclosure information not submitted.

Senior Author(s)

JE

Joanne Edwards, PhD

Professor of Translational Pathology
University of Glasgow
GLASGOW, Scotland, United Kingdom

Disclosure information not submitted.

Purpose/Background: Treatment decisions for colorectal cancer continue to be based on TNM staging and certain pathological features but does not account for any assessment of tumor biology. With increasingly advanced technology available to deeply phenotype the tumor microenvironment (TME), there is an unmet need for biomarkers to guide multimodal decisions. Neoadjuvant systemic regimens are biology-agnostic, with many patients overtreated or without benefit. Tumor-associated macrophages (TAM) are the critical player in directing the TME, historically difficult to assess due to plasticity and oversimplification of the M1/M2 paradigm. The aim of this study was to utilize multiomic approaches to define TAM subtypes that predict cancer-specific survival.

Methods/Interventions: A retrospective highly-curated tissue cohort of patients undergoing curative resection of colorectal cancer was studied. Stage I-IV were included, with those receiving neoadjuvant therapy or died within 30 days of surgery excluded. A tissue microarray (TMA) was established to allow for translational assessment of the microenviroment using chromogenic immunohistochemistry (IHC), bulk RNA sequencing, and multiplex immunofluorescence panels to characterise the phenotype and spatial relationships of TAM's. Subgroup analysis was performed for mismatch-repair proficient status. Visiopharm was used for segmentation and AI-based machine learning. Bioinformatic analysis was performed to determine the associations with cancer-specific survival with 10 years of follow up.

Results/Outcomes: High TAM infiltrate was associated with worse cancer-specific survival, including CD68+, CD163+, or CD68+CD163+ TAM populations. Furthermore, cancer deaths were also associated with high tumoral NFKB (p65) expression, and high CD68+ SPP1+ TAMs. However, interestingly certain TAM phenotypes were associated with improved survival including high CD68+HLA-DR+, and CD68+PD-L1+ TAMs. Additionally, high NFKB activation status within TAM's appears to be favorable.

Conclusion/Discussion: A detailed assessment of tumor-associated macrophages allows for a better stratification of cancer-specific survival. These findings highlight scalable biomarkers that could identify responders to systemic therapy, potential pMMR candidates for immunotherapy and a potential targets for macrophage-directed therapies to complement multidisciplinary care.