Study cracks new insights into ovarian cancer’s immune evasion
Researchers at Weill Cornell Medicine have identified a novel mechanism by which ovarian tumors hinder the immune system’s T cells, blocking their energy supply and limiting their effectiveness against cancer. This discovery, published in Nature, highlights a potential new immunotherapy approach for treating ovarian cancer, a notoriously challenging disease to manage.
The team found that within the tumor’s microenvironment—a network of cells and molecules that protect cancer cells—T cells lose their ability to absorb lipids, which are essential for energy. Senior researcher Dr. Juan Cubillos-Ruiz explained that T cells rely on lipids for fuel, but ovarian tumors disrupt this process by trapping a protein, FABP5, inside T cells. Without access to the cell surface, FABP5 cannot absorb lipids to support T cell activity against the tumor.
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Dr. Sung-Min Hwang, lead author of the study, identified Transgelin 2 as a protein that usually escorts FABP5 to the cell surface. However, ovarian tumors suppress Transgelin 2 production in T cells through the activation of the transcription factor XBP1, effectively blocking lipid uptake and crippling T cell energy.
To address this, researchers engineered CAR T cells with a modified Transgelin 2 gene that resists suppression by the tumor’s stress factors. This enhancement enabled the modified CAR T cells to absorb lipids, resulting in a significantly stronger response against ovarian tumors in preclinical models. This breakthrough points to new strategies for improving T cell-based therapies in solid tumors like ovarian cancer.
This research is supported by the NIH, Department of Defense, and other organizations, and was conducted in collaboration with various external partners to drive forward scientific innovation.
