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Immunofluorescence Analysis of Endogenous and Exogenous Centromere-kinetochore Proteins
Published on: March 3, 2016
Integrative analysis of exogenous, endogenous, tumour and immune factors for precision medicine
Shuji Ogino1,2,3,4, Jonathan A Nowak1, Tsuyoshi Hamada2
1Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Insights
Molecular pathological epidemiology (MPE) integrates tumor immunology with population health to understand how lifestyle and genetics influence cancer immunity. This approach aims to improve precision immuno-oncology and cancer prevention strategies.
Area of Science:
- Oncology
- Immunology
- Epidemiology
- Molecular Pathology
Background:
- Cancer immunotherapy, particularly targeting CTLA4 and PD-1/PD-L1 pathways, is revolutionizing oncology, with precision immuno-oncology showing great promise.
- Exogenous and endogenous factors like diet, lifestyle, and microbiome influence tumor-immune interactions, but integrative analyses are lacking.
- Immune cell analyses within the tumor microenvironment are not adequately integrated into large-scale studies.
Purpose of the Study:
- To introduce and advocate for the transdisciplinary field of molecular pathological epidemiology (MPE) to bridge the gap between tumor immunology and population health sciences.
- To establish research frameworks for integrating tumor immunology into population studies, linking exposures and germline genetics to tumor and immune characteristics.
- To propose an integrated immunology-MPE model for understanding environment-tumor-immune interactions and advancing precision medicine in oncology.
Main Methods:
- Utilizing multilevel research frameworks combining bioinformatics, in vivo pathology, and omics technologies (genomics, epigenomics, transcriptomics, proteomics, metabolomics).
- Analyzing various biological samples including tissue, peripheral blood, plasma, stool, sputum, and urine.
- Synergizing the immunology-MPE model with experimental immunology, microbiology, and systems biology approaches.
Main Results:
- Molecular pathological epidemiology (MPE) provides a framework to integrate tumor immunology into population health sciences.
- The model links exposures and germline genetics (e.g., HLA genotypes) to tumor and immune characteristics.
- Proof-of-principle studies in colorectal cancer demonstrated immunomodulatory effects of factors like aspirin, vitamin D, and omega-3 fatty acids.
Conclusions:
- The integrated immunology-MPE model offers a powerful approach to understand complex environment-tumor-immune interactions.
- This model can significantly contribute to the development of more effective immunoprevention and immunotherapy strategies.
- Advancing precision medicine through a deeper understanding of individual susceptibility and response to cancer therapies and preventive measures.
Abstract:
Immunotherapy strategies targeting immune checkpoints such as the CTLA4 and CD274 (programmed cell death 1 ligand 1, PD-L1)/PDCD1 (programmed cell death 1, PD-1) T-cell coreceptor pathways are revolutionising oncology. The approval of pembrolizumab use for solid tumours with high-level microsatellite instability or mismatch repair deficiency by the US Food and Drug Administration highlights promise of precision immuno-oncology. However, despite evidence indicating influences of exogenous and endogenous factors such as diet, nutrients, alcohol, smoking, obesity, lifestyle, environmental exposures and microbiome on tumour-immune interactions, integrative analyses of those factors and immunity lag behind. Immune cell analyses in the tumour microenvironment have not adequately been integrated into large-scale studies. Addressing this gap, the transdisciplinary field of molecular pathological epidemiology (MPE) offers research frameworks to integrate tumour immunology into population health sciences, and link the exposures and germline genetics (eg, HLA genotypes) to tumour and immune characteristics. Multilevel research using bioinformatics, in vivo pathology and omics (genomics, epigenomics, transcriptomics, proteomics and metabolomics) technologies is possible with use of tissue, peripheral blood circulating cells, cell-free plasma, stool, sputum, urine and other body fluids. This immunology-MPE model can synergise with experimental immunology, microbiology and systems biology. GI neoplasms represent exemplary diseases for the immunology-MPE model, given rich microbiota and immune tissues of intestines, and the well-established carcinogenic role of intestinal inflammation. Proof-of-principle studies on colorectal cancer provided insights into immunomodulating effects of aspirin, vitamin D, inflammatory diets and omega-3 polyunsaturated fatty acids. The integrated immunology-MPE model can contribute to better understanding of environment-tumour-immune interactions, and effective immunoprevention and immunotherapy strategies for precision medicine.
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