Nature Sub-Journal: A New Marker of Cancer Immunotherapy Response

Over the past five years, there have been huge advances in the treatment of blood cancers, thanks to a new type of cancer immunotherapy called CAR-T cell therapy

To understand the molecular mechanisms behind these different responses, researchers from MIT and Harvard's Broad Institute, the Dana-Farber Cancer Institute, and massachusetts general hospital studied blood samples

The authors say their study, published today in Nature Medicine, is part of a broad-partnered collaboration with IBM to study resistance to cancer treatments that could one day help doctors choose the best treatments for their patients and help scientists optimize those treatments to improve response rates

"Understanding the T cell phenotype of CAR-T cells before and after infusion gives us insight into why patients respond or not to this potential life-saving therapy," said Catherine Wu, co-senior author of the study and a member of the Broad Institute, a professor of medicine at Harvard Medical School, and attending physician

In their study, the researchers used single-cell RNA sequencing to analyze gene expression

"By leveraging data from Massachusetts General Hospital and Dana-Farber, as well as the computing framework developed by Broad, we were able to scale this study a lot,

Haradhvala and co-first authors of the study Mark Leick (Massachusetts General Hospital), Katie Maurer (Dana-Farber) and Satyen Gohil (Dana-Farber/Broad), and Gad Getz, co-senior author, member of the Broad Institute and professor of pathology at Harvard Medical School, and internal medicine scientist Catherine Wu, Marcela Maus

"This is a unique opportunity because over time we are able to really gain insight into the expression profile of T cells," Maus said

Track T cells

In CAR-T cell therapy, doctors first collect a sample

In the study, the researchers compared blood samples from patients who received different CAR-T cells (called "axis cell axi-cel" and "histiocyte tisa-cel") for large cell lymphoma, as well as the treatment itself

Using single-cell RNA sequencing, the team studied changes in

These traits gave the team clues

Haradhvala said it is possible for manufacturers to remove CAR-Tregs from engineered cells to reduce the chances of

Next, the team will work to find markers that might indicate which patients experience side effects, such as neurological symptoms or cytokine release syndrome (the immune system's overreaction to immunotherapy

In the meantime, Getz hopes the work will inspire other researchers to conduct similar collaborative studies on other FDA-approved CAR-T therapies