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

Höppener, D. J., Nierop, P. M. H., Hof, J., Sideras, K., Zhou, G., Visser, L., Gouw, A. S. H., de Jong, K. P., Sprengers, D., Kwekkeboom, J., Vermeulen, P. B., Grünhagen, D. J. & Verhoef, C., 18-May-2020, In : British Journal of Cancer. 11 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • 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

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
Number of pages11
JournalBritish Journal of Cancer
Early online date2020
Publication statusPublished - 18-May-2020

    Keywords

  • LONG-TERM SURVIVAL, HEPATIC RESECTION, PROGNOSTIC IMPACT, CANCER PATIENTS, CLINICAL SCORE, T-CELLS, B-CELLS, PATTERNS, THERAPY, OPTION

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