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Tho Pham, MD

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Especialidades médicas y/o especialidades quirúrgicas

Anatomic & Clinical Pathology

Trabajo y educación

Educación

University of California, San Diego, San Diego, CA 92093, 06/30/2009

Primeros años de residencia

Stanford University Pathology Residency, Stanford, CA, 6/30/2010

Últimos años de residencia

Stanford University Hospital and Clinics, Stanford, CA, 6/30/2013

Subespecialidad

Stanford University Hospital and Clinics, Stanford, CA, 6/30/2014

Certificado(s) de especialidad

Anatomic & Clinical Pathology, American Board of Pathology

Blood Banking/Transfusion Medicine, American Board of Pathology

Todo Publicaciones

Normalizing microbiota-induced retinoic acid deficiency stimulates protective CD8+ T-cell-mediated immunity in colorectal cancer Immunity Bhattacharya, N., Yuan, R., Prestwood, T., Penny, H., DiMaio, M., Reticker-Flynn, N., Krois, C., Kenkel, J., Pham, T., Carmi, Y., Tolentino, L., Choi, O., Hulett, R., Wang, J., Winer, D., Napoli, J., Engleman, E. 2016; 45: 64155

Abstract

Although all-trans-retinoic acid (atRA) is a key regulator of intestinal immunity, its role in colorectal cancer (CRC) is unknown. We found that mice with colitis-associated CRC had a marked deficiency in colonic atRA due to alterations in atRA metabolism mediated by microbiota-induced intestinal inflammation. Human ulcerative colitis (UC), UC-associated CRC, and sporadic CRC specimens have similar alterations in atRA metabolic enzymes, consistent with reduced colonic atRA. Inhibition of atRA signaling promoted tumorigenesis, whereas atRA supplementation reduced tumor burden. The benefit of atRA treatment was mediated by cytotoxic CD8(+) Tcells, which were activated due to MHCI upregulation on tumor cells. Consistent with these findings, increased colonic expression of the atRA-catabolizing enzyme, CYP26A1, correlated with reduced frequencies of tumoral cytotoxic CD8(+) Tcells and with worse disease prognosis in human CRC. These results reveal a mechanism by which microbiota drive colon carcinogenesis and highlight atRA metabolism as a therapeutic target for CRC.

View details for DOI 10.1016/j.immuni.2016.08.008

View details for PubMedCentralID PMC5132405