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Cellular and Molecular Biology

Prognostic implications of adaptive immune features in MMR-proficient colorectal liver metastases classified by histopathological growth patterns

British Journal of Cancer volume 126, pages 1329–1338 (2022)Cite this article

Subjects

Abstract

Background

After resection, colorectal cancer liver metastases (CRLM) surrounded by a desmoplastic rim carry a better prognosis than the metastases replacing the adjacent liver. However, these histopathological growth patterns (HGPs) are insufficient to guide clinical decision-making. We explored whether the adaptive immune features of HGPs could refine prognostication.

Methods

From 276 metastases resected in 176 patients classified by HGPs, tissue microarrays were used to assess intratumoral T cells (CD3), antigen presentation capacity (MHC class I) and CD73 expression producing immunosuppressive adenosine. We tested correlations between these variables and patient outcomes.

Results

The 101 (57.4%) patients with dominant desmoplastic HGP had a median recurrence-free survival (RFS) of 17.1 months compared to 13.3 months in the 75 patients (42.6%) with dominant replacement HGP (p = 0.037). In desmoplastic CRLM, high vs. low CD73 was the only prognostically informative immune parameter and was associated with a median RFS of 12.3 months compared to 26.3, respectively (p = 0.010). Only in dominant replacement CRLM, we found a subgroup (n = 23) with high intratumoral MHC-I expression but poor CD3+ T cell infiltration, a phenotype associated with a short median RFS of 7.9 months.

Conclusions

Combining the assessments of HGP and adaptive immune features in resected CRLM could help identify patients at risk of early recurrence.

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Fig. 1: Histopathological growth patterns and immune features assessed in colorectal liver metastasis.
Fig. 2: Association of histopathological growth patterns with outcomes.
Fig. 3: Association of immune features with outcomes grouped by histopathological growth patterns.
Fig. 4: Association of CD3LowMHC-Ihi immune phenotype with outcomes in patients with replacement-type histopathological growth pattern.

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Data availability

The data supporting the results in this manuscript is saved at a server of the Research Centre of the Centre hospitalier de l’Université de Montréal, Montreal, QC, Canada.

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Acknowledgements

We thank L. Rousseau, S. Langevin and J. Bilodeau from the CHUM Hepatopancreatobiliary and Colorectal Cancer Prospective Database & Biobank for patient recruitment, biospecimen handling and maintenance of clinicopathological data; L. Meunier and V. Barès from the CRCHUM histology platform for building the tissue microarray and high-resolution scanning; and A. Cleret-Bohot from the CRCHUM microscopy platform for assistance with automated cell and marker quantification.

Funding

ST is supported by the Université de Montréal Roger des Groseillers Research Chair in Hepatopancreatobiliary Surgical Oncology, the Fond de recherche Québec-Santé, and the Institut du cancer de Montréal. NM is supported by the International Hepato-Pancreato-Biliary Association (IHPBA) Kenneth Warren Research Fellowship and Ethicon Inc. (Johnson & Johnson). JS is supported by a research grant from Surface Oncology, which had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

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Author notes

  1. These authors contributed equally: Nouredin Messaoudi, David Henault.

Authors and Affiliations

  1. Hepatopancreatobiliary Surgery and Liver Transplantation Service, Centre hospitalier de l’Université de Montréal, Montreal, QC, Canada

    Nouredin Messaoudi, David Henault, Eve Simoneau, Zhixia Rong, Richard Létourneau, Marylène Plasse, Michel Dagenais, André Roy, Réal Lapointe, Franck Vandenbroucke-Menu & Simon Turcotte

  2. Cancer Axis, Research Centre of the Centre hospitalier de l’Université de Montréal, Montreal, QC, Canada

    Nouredin Messaoudi, David Henault, Isabelle Cousineau, John Stagg & Simon Turcotte

  3. Department of Surgery, University of Antwerp, Antwerp, Belgium

    Nouredin Messaoudi & Dirk Ysebaert

  4. Department of Surgery, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel) and Europe Hospitals, Brussels, Belgium

    Nouredin Messaoudi & Rastislav Kunda

  5. Pathology Service, Centre hospitalier de l’Université de Montréal, Montreal, QC, Canada

    David Stephen & Geneviève Soucy

  6. Translational Cancer Research Unit (GZA Hospitals and University of Antwerp), Antwerp, Belgium

    Peter Vermeulen

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Contributions

Writing of manuscript draft: NM, DH, PV, ST. Statistical analysis: NM, DH, PV, DY, ST. Data generation: NM, DH, IC, PV, DS, GS, JS, ST. All authors have contributed to data interpretation and critical revision of the manuscript.

Corresponding authors

Correspondence to Peter Vermeulen or Simon Turcotte.

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Competing interests

JS is a permanent member of the scientific advisory board of Surface Oncology and holds stocks of Surface Oncology. ST is receiving non-clinical research funding from Bristol-Myers Squibb, clinical research funding from GlaxoSmithKline, Iovance Biotherapeutics and Turnstone Biologics. All other authors report no conflicts of interest concerning this specific publication.

Ethics approval and consent to participate

This study was approved by the comité d'éthique de la recherche of the Centre hospitalier de l’Université de Montréal, Montreal, QC, Canada. Informed consent of individual patients was obtained. This study was performed in accordance with the Declaration of Helsinki.

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Messaoudi, N., Henault, D., Stephen, D. et al. Prognostic implications of adaptive immune features in MMR-proficient colorectal liver metastases classified by histopathological growth patterns. Br J Cancer 126, 1329–1338 (2022). https://doi.org/10.1038/s41416-021-01667-5

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