Enrichment of the tumour immune microenvironment in patients with desmoplastic colorectal liver metastasis

Diederik J Höppener, Pieter M H Nierop, Joost Hof, Kostandinos Sideras, Guoying Zhou, Lydia Visser, Annette S H Gouw, Koert P de Jong, Dave Sprengers, Jaap Kwekkeboom, Peter B Vermeulen, Dirk J Grünhagen, Cornelis Verhoef*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

38 Citations (Scopus)
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Abstract

BACKGROUND: Patients with resected colorectal liver metastasis (CRLM) who display only the desmoplastic histopathological growth pattern (dHGP) exhibit superior survival compared to patients with any non-desmoplastic growth (non-dHGP). The aim of this study was to compare the tumour microenvironment between dHGP and non-dHGP.

METHODS: The tumour microenvironment was investigated in three cohorts of chemo-naive patients surgically treated for CRLM. In cohort A semi-quantitative immunohistochemistry was performed, in cohort B intratumoural and peritumoural T cells were counted using immunohistochemistry and digital image analysis, and in cohort C the relative proportions of individual T cell subsets were determined by flow cytometry.

RESULTS: One hundred and seventeen, 34, and 79 patients were included in cohorts A, B, and C, with dHGP being observed in 27%, 29%, and 15% of patients, respectively. Cohorts A and B independently demonstrated peritumoural and intratumoural enrichment of cytotoxic CD8+ T cells in dHGP, as well as a higher CD8+/CD4+ ratio (cohort A). Flow cytometric analysis of fresh tumour tissues in cohort C confirmed these results; dHGP was associated with higher CD8+ and lower CD4+ T cell subsets, resulting in a higher CD8+/CD4+ ratio.

CONCLUSION: The tumour microenvironment of patients with dHGP is characterised by an increased and distinctly cytotoxic immune infiltrate, providing a potential explanation for their superior survival.

Original languageEnglish
Pages (from-to)196-206
Number of pages11
JournalBritish Journal of Cancer
Volume123
Issue number2
DOIs
Publication statusPublished - 21 Jul 2020

Bibliographical note

Funding information: All funding for this study was institutional.

Research programs

  • EMC MM-04-20-01

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