Abstract 3128: Immune microenvironment of colorectal tumors and matched liver metastases

Abstract

Abstract Introduction: The presence of tumor-infiltrating lymphocytes, in particular T-cells in the tumor and its microenvironment, has been shown to be associated with prognosis in primary colorectal cancer (CRC) and CRC liver metastases (CLM). In this study we examined T-cell composition in the immune microenvironment in surgical specimens from 64 cases with CRC and resectable CLM. Methods: Patients were enrolled in the Oslo-CoMet randomized trial (NCT 01516710). CRC and corresponding CLM were examined by immunohistochemistry to quantify all T-cells (Ttot) and subpopulations of cytotoxic (CTL), helper (TH), and regulatory T-cells (Treg). Densities of T-cells and subtypes (cells/mm2) were calculated at T-cell hotspots in the invasive margin (IM) and intra-tumoral (IT) locations. Median densities with interquartile ranges were calculated and compared for each region in CRC and CLM. Results (Table 1): The highest density of Ttot was observed in the IM for both primary CRC and CLM, with the density in CLM being two-fold higher than CRC (CLMIM median 2853 cells/mm2 vs CRCIM 1257 cells/mm2; p<0.001). For IT regions, the density of Ttot was much lower than in IM, and slightly higher in CRC compared to CLM (CRCIT median 486 vs CLMIT 332; p=0.02). Examining T-cell subtypes, the differences in CTL and TH mirrored Ttot, with the highest densities in the IM (CLMIM>CRCIM) and lower densities in IT regions (CLMIT<CRCIT). For the Treg, the IM densities were similar, while for IT, again, the density was lower in CLM than CRC. Conclusion: In this study, we analyzed the immune microenvironment in matched CRC and CLM surgical specimens. We are currently analyzing associations with long-term outcome and results will be presented at the conference. Table 1: Median T-cell density (interquartile range).CRCIMCLMIMCRCITCLMITTtot1257 (931 - 1735)2853 (2305 - 3813)486 (285 - 704)332 (189 - 564)CTL497 (315 - 722)1083 (762 - 1426)106 (51 - 209)99 (49 - 219)nsTH759 (584 - 983)1888 (1449 - 2745)348 (192 - 480)198 (118 - 383)Treg222 (155 - 375)233 (126 - 375)ns144 (75 - 225)43 (22 - 82)CRC and CLM densities at each location (IM and IT) were compared using the Mann-Whitney U test. P-values were <0.05 for all comparisons unless indicated by ns. Citation Format: Vegar J. Dagenborg, Serena Elizabeth Marshall, Krzysztof Grzyb, Åsmund A. Fretland, Marius Lund-Iversen, Gunhild M. Mælandsmo, Anne-Lise Børresen-Dale, Anne H. Ree, Bjørn Edwin, Sheraz Yaqub, Kjersti Flatmark. Immune microenvironment of colorectal tumors and matched liver metastases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3128.