Prognostic Immune Scoring Of Colorectal Cancer Liver Metastasis With Mhc Class-I Expression Combined To T Cell Quantification.


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3586 Background: Approximately 80% of patients recur after curative-intent resection of colorectal cancer liver metastasis (CRLM) and systemic chemotherapy. Immune profiling may help prognostication to individualize follow-up and lead to novel therapeutic strategies. We tested whether adding major histocompatibility class I (MHC-I) expression to T cell immune scoring in CRLMs could group patients with distinct prognosis. Methods: Tissue microarray analysis of 391 CRLMs resected in 214 patients (2011-2014) followed prospectively until 10/2017. Each CRLM arrayed with twelve 0.6 mm punch biopsies, 6 at the interface (IF) with normal liver and 6 intratumoral (IT). Automated quantification of CD3+ cells and MHC-I+ surface area stained by immunohistochemistry. We tested associations between immune, clinicopathological, and time to recurrence (TTR) and disease specific survival (DSS) outcome variables. Results: The mean patient age was 62.7 years, 78.5% received pre-operative chemotherapy (mean of 6 cycles), and a median of 2 CRLMs/patient were resected. The median TTR and DSS were 15.4 and 56.7 months, respectively. Pre-operative chemotherapy was associated with higher CD3 infiltration and lower MHC-I expression at IF and IT. Good pathological response to chemotherapy (Rubbia-Brandt TRG score 1-2-3) compared to lack of response (TRG 4-5) was associated with higher CD3 infiltration but no significant difference in MHC-I expression. CD3 immune scoring integrating the IF and IT areas had no prognostic value. MHC-I expression prognostically stratified patients with CD3low but not CD3high CRCLMs. Compared to the rest of the cohort, patients with at least one CD3lowMHC-Ihi CRLM (n = 35, 16.4 %) had significantly shorter median TTR (8.3 vs. 17.1 months, p < 0.001) and DSS (42.6 vs. 61.5 months, p < 0.001). CD3lowMHC-Ihi CRLMs were found in 41.2% of recurrent CRLMs in patients without this type of metastasis at first resection. CD3lowMHC-Ihi CRLM was an independent predictor of poor outcomes by multivariate analysis. Conclusions: CD3lowMHChi CRLMs may identify patients with poorly immunogenic tumors associated with worst outcome and suboptimal response to systemic chemotherapy.
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