Nouredin Messaoudi1,2,3,4, David Henault1,2, David Stephen5, Isabelle Cousineau2, Eve Simoneau1, Zhixia Rong1, Richard Létourneau1, Marylène Plasse1, Michel Dagenais1, André Roy1, Réal Lapointe1, Franck Vandenbroucke-Menu1, Rastislav Kunda4, Dirk Ysebaert3, Geneviève Soucy5, John Stagg2, Peter Vermeulen6, Simon Turcotte7,8. 1. Hepatopancreatobiliary Surgery and Liver Transplantation Service, Centre hospitalier de l'Université de Montréal, Montreal, QC, Canada. 2. Cancer Axis, Research Centre of the Centre hospitalier de l'Université de Montréal, Montreal, QC, Canada. 3. Department of Surgery, University of Antwerp, Antwerp, Belgium. 4. Department of Surgery, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel) and Europe Hospitals, Brussels, Belgium. 5. Pathology Service, Centre hospitalier de l'Université de Montréal, Montreal, QC, Canada. 6. Translational Cancer Research Unit (GZA Hospitals and University of Antwerp), Antwerp, Belgium. peter.vermeulen@gza.be. 7. Hepatopancreatobiliary Surgery and Liver Transplantation Service, Centre hospitalier de l'Université de Montréal, Montreal, QC, Canada. simon.turcotte.chum@ssss.gouv.qc.ca. 8. Cancer Axis, Research Centre of the Centre hospitalier de l'Université de Montréal, Montreal, QC, Canada. simon.turcotte.chum@ssss.gouv.qc.ca.
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.
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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