In exploring an aspect of how killer T cells generate the raw materials required for their proliferation, a Ludwig Cancer Research study has uncovered an unexpected link between the immune cells' metabolism, regulation of gene expression, persistence and functional efficacy that could be exploited using existing drugs to improve cancer immunotherapy.
, and that an extensively characterized metabolic enzyme known as isocitrate dehydrogenase plays a central role in the process," said Ho.—is that genetically or pharmacologically disrupting the enzyme did not hamper the proliferation or function of CD8T cells, as we expected it would. Rather, it led to the transformation of their progeny into memory T cells that are more vigorous and live far longer than their predecessors.
Analysis of how disrupting IDH2 activity affected the T cells revealed a link between an altered profile of metabolites in them and epigenetic regulation of their gene expression, in which the chemical tagging of DNA and its protein packaging dynamically alters chromosome structure to determine the availability of genes for reading.
"Our studies showed that when IDH2 is inhibited by drugs, the cell engages alternative metabolic pathways to compensate," said Jaccard."That naturally alters the types and amounts of metabolites generated in the cell, and some of the metabolites affected by these changes are involved in regulating epigenetic enzymes.
As a result, the chromosomes open up in a way that gives the cells' gene expression machinery access to genes that define memory T cells, triggering their transformation. In the absence of IDH2 inhibition, those genes are kept under wraps, bolstering the terminally exhausted CD8Aside from their practical applications, these findings indicate that reductive carboxylation is not required for the proliferation of CD8T cells, as it appears to be for rapidly growing cancer cells.
Ho says his team now plans to examine how best to sabotage reductive carboxylation to prepare better cells for CAR-T and other adoptive T cell therapies, comparing pharmacologic inhibition with gene editing strategies to that end. He and his colleagues will also explore whether cancer cells adapt to hijack the metabolism and epigenetic regulation of T cells to push them into a less persistent, terminal effector state.
Canada Latest News, Canada Headlines
Similar News:You can also read news stories similar to this one that we have collected from other news sources.
Machine learning analysis of research citations highlights importance of federal funding for basic scientific researchBiomedical research aimed at improving human health is particularly reliant on publicly funded basic science, according to a new analysis boosted by artificial intelligence.
Read more »
University of Chicago to break ground on $815M cancer research centerThe University of Chicago is set to break ground this week on the city's first freestanding facility for cancer care and research.
Read more »
Cancer survivors, patients urge Congress for more research funding and early detection supportThe American Cancer Society estimates nearly two million new cancer cases may be diagnosed this year alone.
Read more »
Cancer survivors and patients urge Congress for more research funding and early detection supportNearly 700 cancer patients, survivors and volunteers from every state are urging Congress to make cancer research and prevention a priority.
Read more »
Jill Biden will visit Seattle to showcase support for cancer researchHer visit will focus on survivors of breast cancer and various childhood cancers.
Read more »
Cancer survivors and patients urge Congress for more research funding and early detection supportNearly 700 cancer patients, survivors and volunteers from every state are urging Congress to make cancer research and prevention a priority.
Read more »