Mohammad Zaidi Wins AHPBA Young Investigator Award

March 2019

Mohammad Zaidi, MD, MS, received the Young Investigator Award at the 2019 Annual Meeting of Americas Hepato-Pancreato-Biliary Association for his presentation, "Intratumoral Interleukin-6 and Myeloid Cell Subsets within the Cholangiocarcinoma Tumor Microenvironment." Dr. Zaidi is a post-doctoral research fellow who works in the labs of Emory surgical oncologist-scientist Shishir Maithel, MD, and Emory cancer immunologist Gregory Lesinski, PhD, MPH. Dr. Maithel and Dr. Lesinski were Dr. Zaidi's mentors on the project.

The study was concerned with cholangiocarcinoma (CC), an aggressive cancer that begins in the bile ducts that is largely resistant to conventional therapy, and focused on the immune tumor microenvironment of the disease, or the immune cells that surround the tumor and how CC changes those cells so that it can grow and spread. In particular, Dr. Zaidi and his team hoped to determine the levels of interleukin-6 (IL-6), an immunomodulating agent that is secreted by CC, and how those levels corresponded to the infiltration of myeloid-derived suppressor cells (MDSCs), a heterogeneous population of cells that suppress T cell responses and can allow cancer to proliferate.

To conduct the study, the investigators used human tissue samples from 69 patients who underwent curative-intent resection of CC from 2000-2015 to create a tissue microarray (TMA), an assemblage of tumor biopsy samples on microscopic slides for analysis. The slides were stained for IL-6, GM-CSF (another immunomodulatory cytokine secreted by CC), and surrogate markers for MDSCs, using immunofluorescent-labeled antibodies. Varying levels of IL-6, GM-CSF, and MDSCs were detected among patients.

Dr. Zaidi and his co-researchers concluded that the study methods provided reliable data, and that the inflammatory biomarkers and immune cell infiltration they observed showed that levels of IL-6 and GM-CSF appeared to correlate with surrogate MDSC mediation of immunosuppression in the tumor microenvironment. The team concurred that targeting IL-6 and/or GM-CSF using inhibitory agents could augment the efficacy of immunotherapy in treating CC, and merited further investigation.