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Study offers way to increase immune checkpoint inhibitor effectiveness in patients with MTAP-deleted cancers

29 Sep 2023
Study offers way to increase immune checkpoint inhibitor effectiveness in patients with MTAP-deleted cancers

Loss of the “housekeeping” gene methylthioadenosine phosphorylase, or MTAP, is a common event in cancer.

Patients with melanoma or bladder cancer whose tumour cells lack a functioning version of the gene tend not to respond to immune checkpoint inhibitors, although the reasons haven’t been clear.

In this study, researchers at Dana-Farber and the University of Texas MD Anderson Cancer Center found that the deletion of MTAP creates a build-up of the protein MTA within tumour cells.

The cells secrete most of the MTA into the extracellular space, where it impedes the growth and activity of cancer-fighting T cells of the immune system.

The researchers hypothesised that MTA-degrading enzymes could reduce MTA levels in the tumour micro-environment, restoring T cell function and improving the effectiveness of immune checkpoint inhibitors.

Tests of this approach in tumour models showed this to be the case: the number of active T cells rose, and tumour growth slumped. 

The deletion of MTAP is primarily responsible for the decline in T cell function and lack of response to immune checkpoint inhibitors in patients whose tumour cells lack working copies of this gene.

Drugs that deplete MTA have the potential to enhance the effectiveness of checkpoint inhibitors in these patients.

Source: Dana-Farber Cancer Institute