Excess fat aids cancer cells in "suppressing" immune cells and hastening tumor g

Posted by beauty33 on January 20th, 2022

Obesity has been linked to an increased risk of dozens of cancers (lung, liver, pancreatic, thyroid, cervical, breast, and colorectal), as well as a worse prognosis and survival, making it one of the most critical public health challenges of the 21st century.

Over time, scientists have identified risk factors connected with obesity, such as metabolic alterations and chronic inflammation, that can lead to tumor growth. The processes underlying the relationships between fat and cancer, on the other hand, are yet unknown.

In a new study, Harvard Medical School researchers and collaborators disclosed the answer: obesity, which is induced by a high-fat diet, permits cancer cells to win the war for metabolic \"fuel\" over immune cells. \"Obesity Shapes Metabolism in the Tumor Microenvironment to Suppress Anti-Tumor Immunity\" is the title of the study, which was published online in the scientific journal Cell.

In this work, researchers provided high-fat diet (HFD) and control diet (CD) to different groups of mice with different types of cancer (lung, breast, colorectal, and melanoma) in order to reveal the effects of obesity on the mice. Obesity-related changes were observed in different cell types and molecules of the tumor microenvironment, both inside the tumor and in its surrounding environment. The results showed that high-fat diet-induced obesity impaired the function of CD8+ T cells (a type of cell that kills cancer cells, virus-infected cells, and other damaged immune cells) in the tumor microenvironment of mice and accelerated tumor growth. This is because cancer cells \"reengineer\" their metabolic mechanisms to adapt to increasing adiposity so that they are better able to \"take energy-rich fat molecules from\" T cells, inhibiting T cell metabolism while accelerating tumor growth. Blocking this fat-related metabolic redesign significantly reduced tumor size and improved anti-tumor immunity in mice passively receiving a high-fat diet.

Meanwhile, the researchers discovered that increasing the expression of prolyl hydroxylase 3, a protein that has been shown to inhibit excessive fat metabolism in normal cells, could effectively reverse the negative effects of a high-fat diet on tumor immune cell function, suggesting that it could be a future therapeutic target for a variety of cancers.

According to Marcia Haigis, co-author of the paper and professor of cell biology at the Blavatnik Institute at Harvard Medical School, \"the findings suggest that a therapy that may be effective in one setting may no longer be effective in another. The findings are critical, given the present global prevalence of obesity and the fact that CD8+ T cells are the primary weapon in immunotherapy, stimulating the immune system to attack cancer. As a result, this discovery has significant theoretical implications and provides new ways for improving such sort of immunotherapy.\"