Immunology-MPE and Immunogenomics

Immunology-MPE (molecular pathological epidemiology) (immuno-MPE, immuno-epidemiology, immunoepidemiology, immunologic MPE) is an integrative field of immunology and MPE for prevention and treatment of many diseases (immuno-prevention, immunoprevention).

To harness host immunity for CRC prevention (e.g., lifestyle modification, cancer vaccine, etc.) and therapy, a better understanding of the key drivers of immune response / reaction to CRC is essential.  However, a substantial gap exists between epidemiologic analyses (of diet and lifestyle) and pathological analyses of immune response to CRC.  Thus, there is a critical unmet need for an integrative evaluation of modifiable dietary and lifestyle factors, and detailed profiling of CRC molecular characteristics and host immunity status in the tumor microenvironment.  To address this need, we are utilizing two longitudinal prospective cohort studies, the Nurses’ Health Study (NHS) and the Health Professionals Follow-up Study (HPFS), with long-term exposure data, information of incident CRC cases and their clinical outcome, and archival cancer tissues.  We examine immune response in the local tumor microenvironment, which cannot be done currently without tumor tissue.  We plan to investigate many different immune cell types including helper T cell, memory T cell, regulatory T cell, cytotoxic T cell, suppressor T cell, B cell, plasma cell, natural killer cell (NK cell), other lymphocytes, myeloid derived suppressor cell (MDSC), neutrophil, eosinophil, basophil, macrophage, histiocyte, dendritic cell, etc.  We are now developing multiplex immunofluorescence assay to interrogate multiple markers in a single tissue section.

We utilize our MPE analytical strategy to investigate the combined role of exposures and immunity in colorectal carcinogenesis and cancer progression.

Commissioned Comment in Lancet 2018, entitled “Immunoscore for (colorectal) cancer precision medicine”, which discusses the paper by the International Immunoscore Project led by Jerome Galon.   This paper discusses “immunology-MPE”.

The integrative paradigm of immunology-MPE (immuno-MPE) has been illustrated (Ogino et al. Gut 2018; freely available worldwide). 

Studies of immunogenomics and immuno-MPE are listed below.

Our recent study (M Song et al. Gut 2016, “Plasma 25-hydroxyvitamin D and colorectal cancer risk according to tumour immunity status”) is a hot topics in news.
(Harvard Gazette)
(New York Times)

Also please see some highlights from this immuno-MPE Lab!

M Song et al. (JAMA Oncology 2016) have shown that marine omega-3 polyunsaturated fatty acid intake is associated with lower risk of colorectal cancer that contains abundant FOXP3+ Treg cells.  This study also used the approach of “nutritional MPE“.

Y Cao et al. (Gastroenterology 2016) have shown that regular aspirin use is associated with lower risk of colorectal cancer with low-level tumor-infiltrating lymphocytes (TILs).  This study also used the approach of “pharmaco-MPE“.

M Giannakis et al. (Cell Reports 2016) have shown a positive correlation between neoantigen load (derived from whole exome sequencing data) and T lymphocytic infiltrates.

Y Masugi et al. (Gut 2016 online) have shown an inverse association between tumor CD274 (PD-L1) expression and FOXP3+ Treg cell density in colorectal cancer, implying mutually alternative mechanisms of immunosuppression.  This is one of the largest study on CD274 (PD-L1) expression in colorectal carcinoma.

L Li et al. (Gastroenterology, online) have shown that inflammatory diets are associated with high risk of colorectal cancer that contains lower levels of intratumor periglandular (stromal) lymphocytes.  This study also used the approach of “nutritional MPE“.

T Hamada et al. (J Clin Oncol 2017) have shown that regular aspirin use after cancer diagnosis is associated with lower mortality of colorectal cancer with lower-level CD274 (PD-L1, PDCD1 ligand 1) expression.  This study also used the approach of “pharmaco-MPE“.

Y Masugi et al. (Cancer Immunol Res, online) have shown that PDCD1LG2 (PDCD1 ligand 2, PD-L2) expression of colorectal cancer is inversely correlated with Crohn’s-like lymphoid reaction, tertiary lymphoid tissue around colorectal carcinoma.

And more!

We presented two talks on immuno-genomics at AACR Tumor Immunology and Immunotherapy Meeting in Oct 2017.

We continue working on the topics.  New papers are forthcoming!