Cell: Harvard Medical School confirmed that obesity suppresses immune cells and accelerates tumor growth

In today's society, with economic development and improvement of living standards, obesity has become a major public health problem worldwide.

In fact, obesity is not only a feature, but also a disease.

Although China is not the country with the highest proportion of obese people, due to its huge population base, China has become the country with the largest number of obese people in the world in recent years.

Over the years, scientists have determined that metabolic changes and chronic inflammation caused by obesity will drive tumor growth, but the interaction between obesity and cancer is still elusive.

On December 9, 2020, researchers from Harvard Medical School and other units published in the top international academic journal Cell titled: Obesity Shapes Metabolism in the Tumor Microenvironment to Suppress Anti-Tumor Immunity (Obesity affects the metabolism in the tumor microenvironment, Thereby suppressing anti-tumor immunity) research papers.

The study shows that obesity can reduce the number of important immune cells CD8+ T cells and anti-tumor activity in tumors.

More importantly, the research team discovered a protein called PHD3.

Definition of obesity

The BMI index, or body mass index, is a commonly used international standard to measure the degree of body weight and health.

Obesity leads to insufficient energy supply of T cells in tumors

In order to reveal the effect of obesity on cancer, the research team conducted research on mouse models with different cancer types.

Further experiments showed that diet-related differences in tumor growth depend in particular on the activity of CD8+ T cells.

Surprisingly, a high-fat diet reduces the presence of CD8+ T cells in the tumor microenvironment, but does not reduce the CD8+ T cells in other parts of the body.

Specifically, under a high-fat diet, cancer cells can reprogram their metabolism to increase fat uptake and utilization, while CD8+ T cells cannot, which eventually leads to the exhaustion of certain fatty acids in the tumor microenvironment, making CD8+ T cells unable to Obtain this necessary energy source.

The first author of the study, Alison E.

Discover potential therapeutic targets

Next, the research team used several different methods, including single-cell gene expression analysis, large-scale protein analysis, and high-resolution imaging.

Among these metabolic changes, PHD3 is of particular interest.

The research team overexpressed PHD3 in cancer cells.

Cyan is tumor tissue, red is CD8+ T cell

Overall, this study found and confirmed that obesity can reduce the number of important immune cells CD8+ T cells and anti-tumor activity in tumors.
This is because cancer cells will reprogram their metabolism in response to the increase in fat, so as to better consume energy-rich fat molecules, deprive T cells of energy supply, and accelerate tumor growth.

More importantly, the research team discovered a protein called PHD3.
PHD3 protein can inhibit excessive fat metabolism.
Overexpression of PHD3 protein can effectively reverse the suppression of tumor immune cells caused by high-fat diet, which is expected to become a new target for cancer treatment.

In recent years, the development of cancer immunotherapy is greatly affecting the lives of cancer patients.
However, cancer immunotherapy does not benefit everyone.
This study shows that there is a metabolic tug-of-war between T cells and tumor cells, and who has the predominance changes with obesity.
This can help scientists start thinking about cancer immunotherapy and combination therapies.

These results also lay the foundation for a better understanding of how obesity affects cancer and the impact of patient metabolism on treatment outcomes.

Original source:

Alison E.
Ringel, et al.
Obesity Shapes Metabolism in the Tumor Microenvironment to Suppress Anti-Tumor Immunity.
Cell, 2020.
DOI: https://doi.
org/10.
1016/j.
cell.
2020.
11.
009.