Jashodeep Datta, MD Receives 2021 SSO Young Investigator Award
The SSO Young Investigator Award has granted $150,000 to 6 researchers since 2016 when the first grant was awarded. The SSO Research and Education Fund, a restricted fund of the former SSO Foundation, supports the Society’s research grant program. The award is intended to promote and recognize translational or clinical research that supports innovative ideas and concepts to improve health outcomes through advances in cancer care. The 2021 Young Investigator Award recipient is Jashodeep Datta, MD from the University of Miami Miller School of Medicine and Sylvester Comprehensive Cancer Center in Miami, FL. The title of his research is “Intercepting Lineage Trajectories of Tolerogenic Myeloid Cells in Pancreatic Cancer.”
Dr. Datta developed an interest in surgical oncology and cancer immunology during his general surgical training at the University of Pennsylvania. As a surgical oncology fellow at Memorial Sloan Kettering Cancer Center, he honed his knowledge in computational genomics and immunogenomics. Following his training, he was recruited to the University of Miami where he has built a practice focused on caring for patients with pancreatic and hepatobiliary cancers. At the same time, he has developed a basic/translational science laboratory in translational cancer immunology and immunogenomics, investigating the intersection between high-risk genomics in pancreatic cancer and its immunologic repercussions, utilizing this understanding to develop novel mechanistic insights into how myeloid-derived suppressor cells (MDSCs) dictate immunosuppressive tumor-stromal-immune crosstalk in the pancreatic tumor microenvironment and obstruct the ability of T-cells to attack and kill tumors.
“Our work shows that certain tolerogenic mechanisms in MDSCs function as ‘master regulators’ of T-cell dysfunction and exclusion in pancreatic cancer,” he explained. “We also observed that the transcriptional kinetics of these signaling pathways in MDSCs depend on distinct lineage trajectories. Our hypothesis suggests that targeting these specific cellular differentiation states might preferentially disrupt tolerogenic signaling in MDSCs and reverse their suppressive effects on T-cell function, thereby rendering chemotherapy and immunotherapy more effective in the treatment of pancreatic cancer.”
To better understand the biomechanics of this hypothesis, Dr. Datta’s grant proposes novel ways to genetically manipulate these specific lineage markers of MDSCs outside the host, transfer these manipulated MDSCs to a mouse model in which the MDSC compartment can be pharmacologically silenced, and examine the ensuing effects on tumor growth and T-cell function. He points out that, “from a therapeutic perspective, we are investigating the feasibility of developing novel ways to target these lineage markers in MDSCs. We are not quite at the stage where we can translate this research to patients, but the premise of delivering novel therapeutics that are, for example, nanoparticle bound, is becoming more mainstream and deliverable to patients.”
Dr. Datta and his team are not just targeting MDSCs, but are targeting specific cellular mechanisms that govern its immunosuppressive activity. He credits earlier studies presented at SSO for laying the foundation of this work. “We and others have shown that the MDSCs mediate chemoresistance and exclude effector immune cells out of the tumor. Therefore, our next step is to identify the critical mechanisms responsible for these effects. If we can intercept these tolerogenic mechanisms before they become full-fledged in the tumor microenvironment, perhaps we can overcome the therapeutic resistance that has plagued pancreatic cancer in the past.”
Dr. Datta hopes this research will lead to novel combination immunotherapies for pancreatic cancer patients. Once researchers identify tolerogenic lineage-specific markers in MDSCs, the development of nano-engineering strategies – or immunonanotheranostics (another arm of Dr. Datta’s research lab) – will deliver specific therapies to target these mechanisms not only in preclinical models, but also in patients. Like other cancers, when it comes to treating pancreatic cancer, one size does not fit all. “We need to study and understand the nuances within the cancer itself and among patients so we can identify which subsets of patients will benefit from these treatments,” explained Dr. Datta. “As we answer more questions, new questions arise. I applaud and thank the SSO for its support of innovative clinical and translational research that approaches these questions in ways that have the potential to save lives. In the end, the goal is to deliver what we learn to patients.”
SSO’s research grant program is supported by the SSO Research and Education Fund. The availability of research grant funding is dependent upon the financial support of SSO members and donors. Please donate generously to ensure that SSO members have an ongoing source of funds for research projects. 100% of your donation supports this program.