Abstract IA28: Molecular pathological epidemiology of risk factors and CRC microbial and immune characteristics

Abstract

Innate and adaptive immunity plays an important role during carcinogenesis and tumor evolution. Evidence indicates that modifiable factors such as aspirin use, physical activity, obesity, smoking, alcohol, diet, and gut microbiota can influence not only cancer risk and outcome but also the human immune system. In addition, tumor molecular pathology and immunity influence each other. Over the past years, molecular pathology and epidemiology has been united to develop the integrative field of molecular pathological epidemiology (MPE). Recently, we have further integrated cancer immunology and MPE, into a new model of “immuno-MPE”. Immuno-MPE utilizes the MPE research framework to test statistical heterogeneity of the differential associations with tumor subtypes, and can decipher the relations between risk factors and subtypes classified by immune response status. We conducted proof-of-principle studies utilizing two large U.S.-nationwide prospective cohort studies (the Nurses' Health Study and the Health Professionals Follow-up Study). We have shown that plasma vitamin D level (Song M et al. Gut 2016), germline genetic variation (IBD risk allele rs11676348) (Khalili H et al. Carcinogenesis 2015), and marine omega-3 polyunsaturated fatty acid intake (Song M et al. JAMA Oncology 2016) are associated with altered risk of specific immune subtypes of colorectal carcinoma. We have also shown that tumor neoantigen loads (Giannakis M et al. Cell Reports 2016), CD274 (PD-L1) expression (Masugi Y et al. Gut 2016), and Fusobacterium nucleatum (Mima K et al. JAMA Oncology 2015) are associated with densities of CD3+, CD8+, CD45RO+, or FOXP3+ T cells or lymphocytic response (eg., Crohn's-like lymphoid reaction, tumor-infiltrating lymphocytes, TILs) in rectal and colon cancer. Recently, we have shown that certain dietary patterns are associated with altered risk of colorectal cancer enriched with F. nucleatum, suggesting interactive carcinogenic roles of food, nutrients, and microflora (microbiome). The immuno-MPE approach can integrate tumor and immune data together with exposure risk factors and outcome. Immuno-MPE can not only give insights on how risk factors can interact with the immune system to modify cancer incidence, recurrence and survival, but also help develop strategies of immunoprevention and immunotherapy for precision medicine.

Citation Format: Shuji Ogino. Molecular pathological epidemiology of risk factors and CRC microbial and immune characteristics. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr IA28.