2021 Grantee: Victoire Cardot-Ruffino, PhD
Dana-Farber Cancer Institute
Research Project: Evaluation of Antitumor Immunity in Human Clinical Trials
Award: 2021 Pancreatic Cancer Action Network Fellowship, funded by The Francois Wallace Monahan Fund in loving memory of Michael Insel
Award Period: July 1, 2021 – June 30, 2023
Dr. Cardot-Ruffino received her bachelor and master’s degree in Biology from the Ecole Normale Supérieure de Lyon in France. She received her PhD in Oncology from the Université Claude Bernard Lyon I in 2019 after studying the effect of TGFbeta produced by the microenvironment in exocrine pancreatic tumors with Dr. Laurent Bartholin. She developed and validated new genetically engineered mouse models to study the effect of TGFbeta in the microenvironment of pancreatic cancer tumors as well as on muscular atrophy.
She arrived in 2020 at the Dana-Farber Cancer Institute to perform postdoctoral work with Dr. Stephanie Dougan. Dr. Dougan was the recipient of the 2012 PanCAN Pathway to Leadership Grant, funded by Celgene Corporation, which supported her as she transitioned from a postdoctoral fellow to an independent researcher. Dr. Cardot-Ruffino is currently working on clinical trial correlates to understand the role of IL-1beta blockade on myeloid-derived suppressor cells, both in circulation and in the pancreatic tumor microenvironment. She is also studying T-cell reactivation in patients treated with chemoradiation and PD-1 blockade to determine how to improve use of immunotherapy in pancreatic cancer.
Dr. Cardot-Ruffino’s project involves understanding how and why investigational immunotherapy options being tested in several clinical trials are effective or ineffective for pancreatic cancer patients. Immunotherapy involves activating a patient’s immune system to recognize and attack their cancer cells, as well as blocking the tumor and its microenvironment’s mechanisms of evading an immune response. This has proven to be exceedingly challenging for pancreatic cancer, with immunotherapy approaches ineffective in most patients to date.
The aims of Dr. Cardot-Ruffino’s project focus on correlative studies of samples from patients who are being treated within two clinical trials. The first trial is a combination immunotherapy approach being tested in a safety study with the aim to become part of PanCAN’s Precision PromiseSM adaptive clinical trial. Dr. Cardot-Ruffino will collect blood, serum and plasma samples from patients with metastatic pancreatic cancer treated with this experimental combination and compare them to samples from patients treated with standard of care chemotherapy outside the trial. Specifically, she is interested in a population of immune cells known as myeloid-derived suppressor cells and hypothesizes that the level of these cells will be reduced upon treatment with the immunotherapy drugs.
For the other trial, patients with pancreatic tumors that are surgically removable or “borderline” surgically removable will be treated with a combination of chemotherapy and radiation with or without the addition of an immunotherapy agent. In this case, Dr. Cardot-Ruffino is analyzing peripheral blood and tumor tissue samples from patients who participated in the trial and focusing on whether “killer” T-cells are present and activated to attack the cancer cells.
Without knowing whether either combination regimen will have clinical benefit, the work conducted by Dr. Cardot-Ruffino will provide critical mechanistic insights into the role of different immunotherapy approaches in pancreatic cancer patients.