[The Dean's Speaker Series] Pancreatic Cancer and Gut Microbiome: From Bench to Bedside

William Cheung Auditorium
Penn Dental Medicine
240 S. 40th Street

Registration: In-person attendance – Free; sign-in required
CE Credits: 1.0 lecture credits

Lecture Description

We found that the cancerous pancreas harbors a markedly more abundant microbiome compared with normal pancreas in both mice and humans, and select bacteria are differentially increased in the tumorous pancreas compared with gut. Ablation of the microbiome protects against preinvasive and invasive pancreatic ductal adenocarcinoma (PDA), whereas transfer of bacteria from PDA-bearing hosts, but not controls, reverses tumor protection. Bacterial ablation was associated with immunogenic reprogramming of the PDA tumor microenvironment, including a reduction in myeloid-derived suppressor cells and an increase in M1 macrophage differentiation, promoting TH1 differentiation of CD4+ T cells and CD8+ T-cell activation. Bacterial ablation also enabled efficacy for checkpoint-targeted immunotherapy by upregulating PD-1 expression. Mechanistically, the PDA microbiome generated a tolerogenic immune program by differentially activating select Toll-like receptors in monocytic cells. These data suggest that endogenous microbiota promote the crippling immunesuppression characteristic of PDA and that the microbiome has potential as a therapeutic target in the modulation of disease progression.

Educational Objectives

To understand the role of gut microbiome in pancreatic cancer. We found that a distinct and abundant microbiome drives suppressive monocytic cellular differentiation in pancreatic cancer via selective Toll-like receptor ligation leading to T-cell anergy. Targeting the microbiome protects against oncogenesis, reverses intratumoral immune tolerance, and enables efficacy for checkpoint-based immunotherapy. These data have implications for understanding immune suppression in pancreatic cancer and its reversal in the clinic.

Speaker

Deepak Saxena, MS. PhD.

Deepak Saxena is a Tenured Professor in the Department of Basic Science and Craniofacial Biology and Director of Microbiome and Metabolism Program at NYU College of Dentistry. He also have secondary appointment in the Department of Surgery at NYU Langone Medical School. He has obtained his PhD in Molecular Microbiology from MS University of Baroda, India and Postdoc training at Faculty of Arts and Science at NYU. He started his laboratory at NYU College of Dentistry 12 years ago and his lab has grown incrementally in both size and in the quality of their work and is now one of the leading microbiome research programs. Dr. Saxena lab has been funded by more than 10 NIH, DOD, AACR and Lustgarten Foundation grants. Currently, his research is focused on effects of electronic cigarette aerosol on oral health and role of gut microbiome in mediating pancreatic inflammation and driving the inflammation-cancer paradigm. He has published exciting work in high impact journals including Nature, Nature Biotechnology, Nature communication, J of Bacteriology, JDR, J of Clinical Microbiology, J of Experimental Medicine, International Journal of Oral Science, and Lab Chip. His work has also appeared in various media outlets including New York Times, Scientific American, Financial Times, NY1 News, Daily News, Men’s Health, NPR, CNN, AADR, Canadian Dental Association, CDA Essential Magazine, and Nova Scotia Dental Association. Dr. Saxena has received various national and international awards. He is an active committee member of various scientific organizations and also serves on various NIH review panel. As a big advocate and supporter of student research program Dr. Saxena is also a Faculty Advisor to Student Research Group at NYU College of Dentistry. He has trained more than 60 dental students, and co-advised international DDS- PhD students. All of his students had participated at national and international meetings, presented their work and received various awards. To translate his research from bench to bedside in 2017, Deepak co-founded Periomicscare LLC, a research spin-off company that aims to create therapeutic microbial ecosystems as biologic drugs for cancer and oral health, on a commercial scale.

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University of Pennsylvania School of Dental Medicine designates this activity for 1.0 continuing education credits.