Recently, there is a major finding that a class of drug in the treatment of leukemia has the unexpected side-effect of boosting immune responses against many different cancers. This make it by inactiving PI3K p110δ that restrains the antitumour immune response. The good news is that because the drugs used in this study are already being used in the clinic, people could see rapid translation of this research into patient benefit.

As p110δ is primarily expressed in leukocytes, drugs against p110δ have not been considered for the treatment of solid tumours. However, it’s reported that p110δ inactivation in mice protects against a broad range of cancers, including non-haematological solid tumours. Investigators  demonstrate that p110δ inactivation in regulatory T cells unleashes CD8+ cytotoxic T cells and induces tumour regression. Thus, p110δ inhibitors can break tumour-induced immune tolerance and should be considered for wider use in oncology.

A major step forward

The new research, published in Nature, reported that such drugs can significantly restrict tumor growth and spread and reduce the chances of relapse for a broad range of cancers.

inhibiting p110δ in mice significantly increased cancer survival rates across a broad range of tumor types, both solid and haematological cancers. For example, mice in which p110δ was blocked survived breast cancer for almost twice as long as mice with active p110δ. Their cancers also spread significantly less and survival after surgical removal of primary breast cancer tumors was also vastly improved, which has important clinical implications for stopping breast cancer from returning following surgery.

p110δ inhibitors can shift the balance from the cancer becoming immune to body’s defenses towards the body becoming immune to the cancer, by disabling regulatory T cells. This provides a rationale for using these drugs against both solid and blood cancers, possibly alongside cancer vaccines, cell therapies and other treatments that further promote tumor-specific immune responses.

Reference:

Inctivation of PI(3)K p110δ breaks regulatory T-cell-mediated immune tolerance to cancer. Nature 510, 407–411