by Christina Crowe
Lalita Shevde-Samant, Ph.D., Professor, Molecular and Cellular Pathology, UAB Department of Pathology, has been awarded a $1.48 million grant over the next three years to study the immune microenvironment of breast cancer, specifically the plasticity of regulatory T cells. The grant, a Level 2 Breakthrough Award from the Breast Cancer Research Program of the Congressionally Directed Medical Research Program of the Department of Defense, is so called because of its potential to, “make an impactful breakthrough and accelerate progress toward ending breast cancer,” Shevde-Samant says.
“With this grant, the Department of Defense is asking that you take steps toward ending breast cancer,” she explains. “It builds on the shoulders of a large body of data that we’ve established over the last few years, and in that way, positions us to take the research to the next level.”
The basic idea behind the research, titled, “Hedgehog Inhibition Disrupts the Immune Privileges of Breast Cancer,” is that cancer cells interact with other cells in their surroundings and adapt to their environment—the “tumor immune microenvironment.” Unlike situations such as infections where the immune system eliminates intruders (bacteria or viruses or other pathogens), with a tumor, the cancer cells take over the immune system and create a tumor-promoting environment.
“Quite simply put, and in a nutshell, we will pivot immune cells that have become tumor-supporting into tumor-killing cells,” she says.
Shevde-Samant’s team will employ an FDA-approved drug used to treat basal cell carcinoma and apply it to breast cancer in a pre-clinical model. What sets this work apart, she says, is that her group has led studies to characterize this drug’s effects on tumor cells, and with this grant funding her team’s work goes beyond that into immune cells because as she explains, “a tumor is not just tumor cells, it’s a mixture of cells including immune cells.” “We’re looking at harnessing this pathway in the immune cells so we can make them cytotoxic [tumor-killing] versus them being more protective of the tumor.”
This work compliments ongoing research in Shevde-Samant’s lab, in which they study tumor cells to understand how they’re capable of evading therapy. Shevde-Samant says the assays in her experiments take about a month or sometimes more from start to finish, but initial changes can be registered within the first few weeks.
“You don’t want to manipulate just the tumor cells, you also want to disable the immune cells. If you can do both, you have a better chance at moving toward more effective management of cancer.,” she says.
Shevde-Samant is a breast cancer immunologist by training and completed a post-doctorate program in cancer biology, specifically metastasis, which as a whole allowed her to develop, “a very comprehensive perspective on tumor biology.” She started her independent research lab in cancer biology and metastasis in 2004 and about 15 years ago made the decision to incorporate immunology into her research again, she says. At the time, immunotherapy was getting a great deal of attention, so in 2013, she applied for a Department of Defense Breakthrough Level 1 award to undertake a project on breast cancer immunology — which was funded. That research laid the groundwork for subsequent grants including her current project, she says.
Her UAB collaborators on the grant are Rob Welner, Ph.D., Associate Professor, Division of Hematology and Oncology, and Dongquan Chen, Ph.D., Associate Professor, Division of Preventive Medicine, both in the Department of Medicine.