According to the world health organization (WHO), Cancer is the second leading cause of death globally, accounting for an estimated 9.6 million deaths, or one in six deaths, in 2018. Cancer cells multiply abnormally and function incorrectly, go beyond their boundaries to invade adjoining parts of the body and spread to other organs. The latter process is called metastasizing and is a major cause of death. Understanding how cancer cell evade the immune system is a series of puzzles, like
1. Why immune cells behave abnormal?
2. How histones are altered within immune cells? and
3. How a cell’s metabolism processes amino
A study found connecting these puzzles that suggests targeting the amino acid methionine transporter in tumour cells could make immunotherapy effective against more cancers.
Weiping Zou, M.D., Ph.D., Charles B. de Nancrede Professor of Surgery, Pathology, Immunology, and Biology at the University of Michigan and director of the Center of Excellence for Immunology and Immunotherapy at the U-M Rogel Cancer Center. Zou is a senior author on a paper published in Nature that includes multiple labs from the Rogel Cancer Center and collaborators from Poland.
T cells or T Lymphocytes play a central role in cell-mediated immunity. Cancer can turn these cells abnormal, preventing T cells from mounting an attack against it.
What causes this?
A study has been done specifically, how tumours metabolize amino acids. They found an amino acid called methionine had the most impact on T cell survival and function. Low level of methionine alters histone pattern and leads to impaired T cells. When tumour cells come into the picture it fights against T cells and takes methionine, which makes T cells render and ineffective.
In an earlier study a systemic approach to starve tumour cells of methionine, with the idea that the tumour cells are addicted to it. But, Zou says, this study shows why that approach may be a double-edged sword.
“You have competition between tumour cells and T cells for methionine. The T cells also need it. If you starve the tumour cells of methionine, the T cells don’t get it either. You want to selectively delete the methionine for the tumour cells and not for the T cells,” Zou says.
The study found that supplementing with methionine not only restored T cell function but also a high level of methionine will serve both tumour cells and T cells.
Researchers found that tumour cells have more transporters that deliver methionine, impairing those transporters resulted in healthier T cells as the T cells could compete for methionine.
To advance this work Zou was awarded a $3.2 million grant from the National Cancer Institute.
“There are still a lot of mechanistic details not worked yet, particularly the detailed metabolic pathways of methionine metabolism, and how it differs from tumour cells and T cells? We hope to find a target that is relatively specific to tumour cells so that we do not harm the T cells but impact the tumour,” Zou says. This work will be the focus of the new grant.