Abstract 5533: The difference of immune microenvironment betweende novometastatic and non-metastatic microsatellite instability-high colorectal cancer

Abstract

Abstract Introduction: Microsatellite instability-high (MSI-H) colorectal cancer (CRC) consists of 15% of all CRC but only 2-4% of metastatic CRC. The favorable prognosis of non-metastatic (early-stage) MSI-H CRC may be related to vigorous immune reaction in tumor microenvironment. However, the mechanisms of immune evasion in metastatic (late stage) MSI-H CRC are largely unknown. Materials and Methods: We retrospectively collected patients with MSI-H CRC from National Taiwan University Hospital and Kaohsiung Chang Gung Memorial Hospital. The archival tumor specimens were used for immune cells analysis by Nanostring PanCancer Immune Panel, and spatial immune characterization by multiplex immunofluorescence stains. Only surgical resected primary tumors and metastatic tumors were included. Gene expression and immune cells composition were compared between non-metastatic and de novo metastatic tumors. Results: We enrolled 59 and 27 patients with early-stage and late-stage MSI-H CRC, respectively. Twelve metastatic site tumors were also collected. The clinicopathologic characteristics between patients who have early- and late-stage MSI-H CRC were not significantly different. There are heterogeneous immune cell compositions in these 98 MSI-H tumors. Compared to early-stage MSI-H tumors, there are significantly fewer cytotoxic (difference -0.497, p = 0.001) and dendritic cells (difference -0.528, p = 0.021) in late-stage MSI-H tumors. Gene set enrichment analysis disclosed significantly decrease in the expression of JAK-STAT-IFN-γ- and antigen processing-related pathways in late-stage MSI-H tumors. The top 5 genes with significantly differential expression between late-stage and early-stage tumors are C7, TNFRSF12A, MFGE8(up-regulated) and CXCL5, IFNL1, GZMH, HMGB1 and CXCR1 (down-regulated). Conclusions: There are significantly fewer cytotoxic and dendritic cells in late-stage MSI-H CRC, compared to early-stage MSI-H CRC, which is associated with decrease expression in JAK-STAT-IFN-γ- and antigen processing-related pathways. Citation Format: Kuo-Hsing Chen, Chia-Lang u Hs, Yu-Li Su, Chang-Tsu Yuan, Jia-Huei Tsai, Yi-Hsin Liang, Ann-Lii Cheng, Kun-Huei Yeh. The difference of immune microenvironment betweende novometastatic and non-metastatic microsatellite instability-high colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5533.