Stephanie K. Dougan, PhD, assistant professor, Microbiology and Immunobiology, Division of Immunology, Harvard Medical School, researcher, Dana-Farber Cancer Institute, discusses ways of augmenting T-cell immunity in pancreatic cancer.
The current standard of care for patients with pancreatic cancer is combination chemotherapy, such as FOLFIRINOX or gemcitabine and nab-paclitaxel (Abraxane). However, the prognosis remains poor, notes Dougan. Though immunotherapy has been examined in the space, it has not seen much success, prompting investigators to examine ways to augment T-cell priming. Checkpoint blockade operates by de-inhibiting T cells, thereby taking the breaks off the immune system. The contingency with this approach is that the patient has T cells to begin with, which is not true of all malignancies, says Dougan.
Dougan and her fellow investigators have found that activating a small molecule can induce noncanonical NF-kB2 signaling. By augmenting co-stimulation through TNF family receptors, T cells are given a signal. This ultimately enables the priming of T cells that harbor less abundant antigens, states Dougan.