Researchers at Weill Cornell Medicine have identified a mechanism by which ovarian tumors inhibit immune cells, specifically T cells, from mounting an effective attack. Published on October 23 in Nature, the study highlights how ovarian tumors disrupt the energy supply that T cells require to function.
The research reveals that the tumor microenvironment obstructs T cells' ability to utilize lipids, which are essential for their energy. The protein fatty acid-binding protein 5 (FABP5) is crucial for lipid uptake; however, it becomes trapped in the cytoplasm of T cells within the tumor environment, preventing energy acquisition necessary for an immune response.
Key findings indicate that the protein Transgelin 2, which aids in the transport of FABP5 to the cell surface, is suppressed in T cells infiltrating ovarian tumors. This suppression is linked to the activity of the transcription factor XBP1, which is activated under the stress conditions present in tumors.
In an effort to enhance the efficacy of immunotherapy, particularly chimeric antigen receptor T (CAR T) cells, researchers modified the Transgelin 2 gene to resist repression by stress factors. This modification enabled CAR T cells to effectively utilize lipids and mount a stronger attack against ovarian tumors in mouse models.
The findings suggest a promising new direction for immunotherapy in treating aggressive solid tumors, indicating that overcoming this barrier could significantly improve treatment outcomes for ovarian cancer patients.