Study Finds Drug Bypasses Suppressive Immune Cells to Enhance Immunotherapy

In a recent study published in the journal Nature, by recruiting the immune system to combat tumor cells, immunotherapy has improved survival rates, offering hope to millions of cancer patients. However, only about one in five people responded favorably to these treatments.

With a goal of understanding and addressing immunotherapy’s limitations, researchers at Washington University School of Medicine in St Louis have found that the immune system can be its own worst enemy in the fight against cancer.

Cancer vaccines represent a new approach to personalised cancer immunotherapy. Aimed at the mutant proteins specific to a patient’s tumour, such vaccines induce killer T cells to attack tumour cells while leaving healthy cells unharmed. Schreiber’s group previously showed that more effective vaccines also activate helper T cells, another immune cell type, that recruit and expand additional killer T cells to destroy the tumours. But when they tried to add increased amounts of the helper T cell target to supercharge the vaccine they found that they had generated a different type of T cell that inhibited rather than promoted tumour rejection.

Tr1 cells normally put the brakes on the immune system to prevent it from attacking the body’s healthy cells. But their role in cancer has not been seriously explored. Looking through previously published data, the researchers found that tumours from patients who had responded poorly to immunotherapy had more Tr1 cells compared with tumours of patients who had responded well. The number of Tr1 cells also increased in mice as tumours grew bigger, rendering the mice insensitive to immunotherapy.

It is concluded that the drug effectively circumvents the suppressive immune cells that often hinder the effectiveness of immunotherapy. By doing so, it significantly enhances the ability of the immune system to target and destroy cancer cells, potentially improving the overall efficacy of immunotherapy treatments.

References: Awwad, M. & North, R. J. Immunologically mediated regression of a murine lymphoma after treatment with anti-L3T4 antibody. A consequence of removing L3T4+ suppressor T cells from a host generating predominantly Lyt-2+ T cell-mediated immunity. J. Exp. Med. 168, 2193–2206 (1988).