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Integrative analysis of exogenous, endogenous, tumour and immune factors for precision medicine
  1. Shuji Ogino1,2,3,4,
  2. Jonathan A Nowak1,
  3. Tsuyoshi Hamada2,
  4. Amanda I Phipps5,6,
  5. Ulrike Peters5,6,
  6. Danny A Milner Jr7,
  7. Edward L Giovannucci3,8,9,
  8. Reiko Nishihara1,3,4,8,10,
  9. Marios Giannakis4,11,12,
  10. Wendy S Garrett4,11,13,
  11. Mingyang Song8,14,15
  1. 1 Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
  2. 2 Department of Oncologic Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA
  3. 3 Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
  4. 4 Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA
  5. 5 Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
  6. 6 Department of Epidemiology, University of Washington, Seattle, Washington, USA
  7. 7 American Society for Clinical Pathology, Chicago, Illinois, USA
  8. 8 Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
  9. 9 Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
  10. 10 Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
  11. 11 Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA
  12. 12 Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
  13. 13 Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
  14. 14 Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts, USA
  15. 15 Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
  1. Correspondence to Dr Shuji Ogino, Program in MPE Molecular Pathological Epidemiology, Brigham and Women’s Hospital, Boston, MA 02215, USA; shuji_ogino{at}dfci.harvard.edu

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.

  • cancer epidemiology
  • cancer Immunobiology
  • colorectal carcinoma
  • cancer prevention
  • molecular pathology

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Footnotes

  • Contributors RN, MG, WSG and MS contributed equally. SO developed the main concept of the manuscript. SO, AIP, UP and RN wrote grant applications. All authors contributed to review and revision, and approved the final manuscript.

  • Funding This work was supported in part by grants from the USA National Institutes of Health (R35 CA197735 (to SO), K07 CA172298 (to AIP), U01 CA137088 (to UP) and K07 CA190673 (to RN)) and Nodal Award (to SO) from the Dana-Farber Harvard Cancer Center.

  • Competing interests None declared.

  • Provenance and peer review Commissioned; externally peer reviewed.

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