Unique Characteristics of the Tumor Immune Microenvironment in Young Patients with Metastatic Colorectal Cancer

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2023 Dec 28

PMID 38152402

Authors

Brian D Griffith

Jenny Lazarus

Jake McGue

Santhoshi Krishnan

Michael I DAngelica

Jinru Shia

Irina Dobrosotskaya

Jaiqi Shi

Jacob Edwards

Arvind Rao

Timothy L Frankel

Affiliations

Soon will be listed here.

Abstract

Introduction: Metastatic colorectal cancer (mCRC) remains a common and highly morbid disease, with a recent increase in incidence in patients younger than 50 years. There is an acute need to better understand differences in tumor biology, molecular characteristics, and other age-related differences in the tumor microenvironment (TME).

Methods: 111 patients undergoing curative-intent resection of colorectal liver metastases were stratified by age into those <50 years or >65 years old, and tumors were subjected to multiplex fluorescent immunohistochemistry (mfIHC) to characterize immune infiltration and cellular engagement.

Results: There was no difference in infiltration or proportion of immune cells based upon age, but the younger cohort had a higher proportion of programmed death-ligand 1 (PD-L1) expressing antigen presenting cells (APCs) and demonstrated decreased intercellular distance and increased cellular engagement between tumor cells (TCs) and cytotoxic T lymphocytes (CTLs), and between TCs and APCs. These trends were independent of microsatellite instability in tumors.

Discussion: Age-related differences in PD-L1 expression and cellular engagement in the tumor microenvironment of patients with mCRC, findings which were unrelated to microsatellite status, suggest a more active immune microenvironment in younger patients that may offer an opportunity for therapeutic intervention with immune based therapy.

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