Abstract C132: Fusobacterium nucleatum in colorectal carcinoma and expression of multiple immune checkpoint molecules on T cells

Abstract

Abstract Background: Fusobacterium nucleatum (Fn) appears to play a role in colorectal cancer carcinogenesis through suppression of antitumor immune response. This study aims to characterize immune-related signatures, including the expression of multiple immune checkpoint molecules in tumor-infiltrating T cells. Methods: We measured Fn DNA by quantitative PCR in a total of 155 colorectal cancer tissues. Gene expression profile was studied using microarray technology to determine the consensus molecular subtypes (CMS) and immune-related signatures using CIBERSORT and Gene Set Enrichment Analysis (GSEA), respectively. Expression of immune checkpoint molecules (PD-1, TIM-3, and TIGIT) on CD8+ cytotoxic T cells and the ratio of FOXP3-CD4-/FOXP3+CD4 were examined using multicolor flow cytometric analysis. Results: All patients had stage III disease underwent curative surgery. Fn infection was observed in 43% of patients and was associated with recurrence (Fisher’ exact test, P=0.002) and decreased overall survival (log-rank test, P<0.001). The distribution of CMS subtypes was CMS1/2/3/4/mixed (14%/24%/15%/27%/20%), which is comparable to previous data. Fn infection was associated with the platinum-resistant signature, hypoxia pathway, and stem cell pathways in the GSEA. Interestingly, Patients with Fn infection showed a trend toward enrichment in CMS4, mesenchymal subtype with the inflamed immune phenotype (9% vs. 17% with Fn-infection, P=0.24). The number of cytotoxic CD8+ T cells showed a trend toward decreased expression in patients with Fn infection. Furthermore, higher expression of inhibitory immune checkpoints (PD-1, P<0.01; TIM-3, P<0.05; TIGIT, P<0.05) was observed on CD8+ cytotoxic T cells of patients with Fn infection, compared to that of Fn negative cases. Besides, the regulatory FOXP3+CD4+ cells were increased in patients with Fn infection, supporting the suppressive role of Fn infection in the tumor immune microenvironment (P<0.05). Conclusions: The adverse prognostic impact of Fn infection depends on the suppression of T cell-mediated immune response by increased expression of inhibitory immune checkpoints on cytotoxic T cell and by increased regulatory T cells. Citation Format: Han Sang Kim, Wonkyu Kim, Chang Gon Kim, Jinseon Yoo, Soonmyung Paik, Eui-Cheol Shin, Tae-Min Kim, Hoguen Kim, Joong Bae Ahn. Fusobacterium nucleatum in colorectal carcinoma and expression of multiple immune checkpoint molecules on T cells [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr C132. doi:10.1158/1535-7163.TARG-19-C132