Researchers at the GRU Cancer Center of Georgia Regents University in Augusta, Georgia have identified a way to boost the immune system’s efficacy against cancer. Often immune therapies are stunted due to an increase in immune cells called regulatory T cells (Tregs), which suppress immune responses. Being able to inhibit Tregs without affecting other immune cells has been an ongoing challenge to the development of anticancer immunotherapies. Published in Cancer Immunology Research, a study led by Dr. Samir Khleif, GRU Cancer Center Director, presents a promising new approach.
Dr. Khleif’s group discovered that targeting the PI3K-Akt pathway in human and in mouse cells selectively inhibited the activation and proliferation of Tregs – with minimal effect on conventional T cells (Tconv). Studies using in vivo mousemodels evaluated the therapeutic efficacy of Akt and PI3K inhibitors on the antitumor immune response. Selective inhibition of Treg by these inhibitors led to reduced tumor growth. Importantly, when Akt and PI3K inhibitors were used in combination with a cancer vaccine, antitumor immune responses were enhanced through diminished Treg levels. This research provides experimental evidence of a potentially strong strategy to enhance immune responses against cancer. The investigators are in the process of planning clinical trials to use PI3K-Akt pathway inhibitors as immune modulators in combination with cancer immune therapy regimes.
Abu-Eid R1, Samara RN2, Ozbun L3, Abdalla MY4, Berzofsky JA5, Friedman KM6, Mkrtichyan M1, Khleif SN7. Selective inhibition ofregulatory T cells by targeting PI3K-Akt pathway. Cancer Immunol Res. 2014 Jul 30. pii: canimm.0095.2014. [Epub ahead of print]