Breakthrough research targets immunotherapy resistance
Weiyi Peng, M.D., Ph.D., assistant professor of Melanoma Medical
photo by Wyatt McSpadden
Stories of immunotherapy’s success against metastatic melanoma in patients such as former President Jimmy Carter are well publicized, but the treatment doesn’t work for everyone.
In fact, checkpoint blockade drugs such as pembrolizumab and nivolumab, which inhibit protein molecules on T cells that keep the immune system from attacking tumors, only work for about one-third of patients.
Why do some tumors respond to immunotherapy and others don’t? That’s a question MD Anderson’s Weiyi Peng, M.D., Ph.D., and her team of investigators are getting closer to answering.
Peng, an assistant professor in Melanoma Medical Oncology, led a study that showed a link between the loss of a tumor-suppressor gene called PTEN and resistance to checkpoint inhibitor immunotherapy.
Patients with inactive PTEN had fewer T cells in their tumors, indicating that a lack of PTEN suppresses the immune response against melanoma. Patients with inactive PTEN also had worse outcomes when treated with checkpoint inhibitors compared to melanoma patients with intact PTEN.
These findings indicate PTEN loss may be an important biomarker to predict melanoma patients’ resistance to immunotherapy. The study also showed that treatment with an experimental drug that blocks a molecular pathway called PI3K improved the effectiveness of anti-PD-1 treatment in laboratory models of melanomas with loss of the PTEN gene.
“These results allowed us to devise a means of combating resistance to immunotherapy due to PTEN loss in melanoma patients,” Peng says.