A new approach to understanding why T-cells are often too weak to fight and destroy tumor cells has earned Yale Cancer Center researchers team science award from the Sokoloff Family-Melanoma Research Alliance (MRA).
The $900,000 award will fund research over three years examining metabolic regulation of tumor immune response by the microenvironment. The team includes Marcus Bosenberg, M.D., PhD, associate professor of dermatology and pathology, Susan Kaech, PhD; Richard Kibbey, M.D., PhD; and Sidi Chen, PhD. The experiments proposed required the diverse expertise of team members, which includes melanoma biology, immunology, metabolism, and genomic techniques.
“Melanoma has touched our family directly,” said Jonathan Sokoloff. “More progress has been made in the fight against melanoma in the past five years than in the prior fifty. We are proud to partner with Yale to help advance research in this fast developing field.”
The MRA says the team science award is the centerpiece of its funding portfolio. The award’s primary aim is to foster collaborative research among multidisciplinary teammates with complementary expertise.
“We thank the Sokoloff family and the MRA for this generous award and for their continued support of new approaches to this lethal and common form of cancer,” Marcus Bosenberg said. “We believe our idea presents an entirely different perspective on how immunosuppression may be generated within tumors”
Kaech, a professor of immunobiology, said that cancer cells consume nearly all the nutrients, like sugar and amino acids, inside the tumor environment, leaving the T-cells deprived of nutrients and energy, and unable to function properly. Since cancer cells consume such large amounts of nutrients to grow and multiply, they hypothesize that this causes a metabolic tug-of-war within the tumors that the T-cells ultimately lose.
To explore this theory, they will examine what T-cells “eat” in tumors to better understand how this affects anti-tumor defenses. Then, they will try to rewire the metabolic activities of T- cells to improve function in nutrient-poor conditions.
“To our knowledge, this work is the first to examine these types of questions and offers untapped potential for the development of new therapies or drugs that can enhance a T cell’s attack on tumors through metabolic manipulation” Bosenberg said. “Given that obesity and other metabolic diseases, like Type 2 diabetes, are reaching epidemic proportions, there is a huge focus to find drugs that regulate cellular metabolism to treat these diseases. It is likely that some of these drugs would affect T-cell metabolism and enhance anti-tumor immunity, and could be repurposed for novel cancer treatments.”