Abstract IA019: Molecular pathological epidemiology of tumor microbiota and immunity can give etiologic insights

Abstract

Abstract This lecture discusses the integration of tumor microbiology and immunology into evolving/expanding molecular pathological epidemiology (MPE) research framework (Ogino et al. Gut 2011; Ogino et al. Annu Rev Pathol 2019; Inamura et al. Gut 2022; etc.), which will open new opportunities. Neoplasms represent heterogeneous pathological processes due to interactive influences of the exposome (including the microbiome), the immune system, and neoplastic cells. Hence cancers should be regarded as not only microenvironmental diseases but also environmental and systemic diseases (Inamura et al. Gut 2022). To address this complexity, we investigate influences of exposures on microbial-tumor-immune interactions in tumor microenvironment. Colorectal cancer (CRC) provides an ideal model, as the colorectum is the most microbial rich organ and there are many established or putative risk factors for CRC. In our proof-of-principle studies that used the Nurses’ Health Study and Health Professionals Follow-up Study along with tumor tissue biobanks having 1700 CRC cases, we can provide evidence for influences of prudent diets (Mehta et al. JAMA Oncol 2017), inflammatory diets (Liu et al. Clin Gastroenterol Hepatol 2018), and western diets (Arima et al. Gastroenterology 2022) on developments of cancer subtypes with intratumor bacteria such as Fusobacterium nucleatum and pks+ Escherichia coli. We have also gain insights into interactions between microbes and immune cells. We have discovered an inverse relationship between F. nucleatum and T cell infiltrates (Mima et al. JAMA Oncol 2015), especially CD3+CD4+CD45RO+ memory helper T cells (Borowsky et al. Clin Cancer Res 2021). In situ spatial single cell analyses using multispectral fluorescence imaging and machine learning can shed light on the roles of microbes as well as various immune cell infiltrates in CRC (Vayrynen et al. Cancer Immunol Res 2021; Vayrynen et al. J. ImmunoTher Cancer 2021; Vayrynen et al. Cancer Immunol Res 2022; Akimoto et al. Front Immunol 2022). The integrative MPE approach is also expected to advance research on early-onset cancers (Akimoto et al. Nat Rev Clin Oncol 2021; Ugai et al. Nat Rev Clin Oncol, in press). Our new research paradigm to integrate microbial and immune assays on archival tumor tissue in large-scale population studies can provide not only etiological insights but also possible paths for precision medicine and prevention. Citation Format: Shuji Ogino. Molecular pathological epidemiology of tumor microbiota and immunity can give etiologic insights [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer; 2022 Oct 1-4; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_1):Abstract nr IA019.