An emerging class of anticancer drugs called EZH2 inhibitors may greatly enhance the potency of some cancer immunotherapies, according to a preclinical study led by Weill Cornell Medicine lymphoma researchers.
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T-cell immunotherapies, including modified anti-cancer T cells called CAR-T cells, have been shown to reduce or eliminate signs of cancer in some patients with lymphomas and other malignant blood tumors. In most cases, however, signs of cancer eventually reappear. A study published in Cancer Cell suggests that inhibiting EZH2 could help improve the potency and durability of these immunotherapies. EZH2 is an enzyme that normally helps program cellular behavior by controlling the expression of specific genes. Mutations in the EZH2 gene, which make the enzyme more active, are now recognized as common features of lymphoma, and inhibition of this enzyme has been shown to benefit lymphoma patients even when they have non-mutant EZH2. In the study, the researchers found that EZH2 inhibition enhanced the effects of immunotherapies not only by making lymphoma cells more visible to them, but also through multiple other mechanisms, including reducing immunosuppressive regulatory T cells and reprogramming anti-cancer T cells in a way that makes their activity more durable.