430. Tumor microbiota and tumor-infiltrating T cells in the tumor microenvironment of colorectal cancer

Abstract Background Recent studies indicate that the gut microbiota influences the immune cell infiltrates in colorectal cancer. For example, a study has shown that the amount of Fusobacterium nucleatum in colorectal carcinoma has been inversely associated with CD3+ cell density in tumor. Evidence also indicates that Bacteroides fragilis may suppress the adaptive T cell response. Based on such biological evidence, we hypothesized that T cell infiltrates might differ by the colorectal tumor tissue microbiota. Methods We conducted 16s rRNA sequencing to identify the abundance of 1,518 microbiome species in 861 colorectal cancer patients in the Nurses’ Health Study and the Health Professionals Follow-up Study. Multiplex immunofluorescence combined with digital image analysis and machine learning algorithms was used to measure various T-cell subsets, such as CD3, CD4, and CD8. Spearman correlation test was performed to investigate the association between the abundance of gut microbiota and CD3+, CD3+CD4+, and CD3+CD8+ T-cell densities in the overall tumor region. For the validation, we used tumor microbial data by qPCR. Results The strongest negative association was observed between the genus Clostridium and CD3+CD4+ T-cell density (rho = -0.13, p=8.27E-05). Bacteroides fragilis had a statistically significant negative association with CD3+ T-cell density (rho = -0.10, p = 0.0026) and CD3+CD4+ T-cell density (rho = -0.12, p < 0.001). Fusobacterium nucleatum also had a significant negative association with CD3+ T-cell density (rho = - 0.078, p = 0.021) and CD3+CD4+ T-cell density (rho = -0.11, p = 0.0011). These findings were validated by analyses using qPCR data. Conclusion We identified tumor microbiota, the abundance of which was inversely associated with tumor-infiltrating T cells in the tumor microenvironment of colorectal cancer. The strongest negative association was observed between Clostridium and CD3+CD4+ cell density. The abundance of Bacteroides fragilis and Fusobacterium nucleatum correlated negatively with the density of CD3+ and CD3+CD4+ cells in colorectal carcinoma tissue. Our findings provide new evidence for microbial-immune interactions in the tumor microenvironment. Disclosures All Authors: No reported disclosures