The Role of TSLPR+ST2+ Tregs in Colorectal Cancer

Colorectal cancer (CRC) is the second most common cause of cancer-related deaths in the world. In the US, CRC is the third most common cancer, affecting 1-2% of the adult population. Importantly, treatments have not been sufficient for all the patients with CRC to recover, immune checkpoint inhibitors (ICIs) are effective only for less than 5% of patients, demonstrating the need for additional therapeutics.

We recently discovered a novel subset of regulatory T cells (Tregs) that co-express the receptors for TSLP and IL-33 (TSLPR+ST2+ Tregs) in tumors, but not uninvolved colon, from patients with CRC. Using mouse models, we showed that loss of TSLP signaling by these Tregs led to dramatically reduced tumor progression, as did treatment with a neutralizing anti-TSLP antibody.

This TSLPR+ST2+ Treg has the potential to be a diagnostic marker (as we find this subset in blood of CRC patients) and a therapeutic target for colorectal cancer. We are now studying the development and function of this novel Treg subset in the context of colorectal cancer.