News Release 12-Apr-2021

Editor’s note: Moderate physical exercise is important for cancer patients. But all means you need to do exercise everyday. It is not just for immunity, not just for treatments. At least it is also for neutralizing inflammation. Exercise improves your odds of survival.

編者註：適度的體育鍛煉對癌症患者很重要。 但是，所有這些都意味著您需要每天鍛煉。 這不僅是為了免疫，也不只是為了治療。 至少它還用於中和炎症。 鍛煉可以提高您的生存機率。

Tumors grew more slowly and responded better to immunotherapy in mice that exercised compared with sedentary mice.

Massachusetts General Hospital

Research News

BOSTON – Exercise training may slow tumor growth and improve outcomes for females with breast cancer – especially those treated with immunotherapy drugs – by stimulating naturally occurring immune mechanisms, researchers at Massachusetts General Hospital (MGH) and Harvard Medical School (HMS) have found.

Tumors in mouse models of human breast cancer grew more slowly in mice put through their paces in a structured aerobic exercise program than in sedentary mice, and the tumors in exercised mice exhibited an increased anti-tumor immune response.

“The most exciting finding was that exercise training brought into tumors immune cells capable of killing cancer cells known as cytotoxic T lymphocytes (CD8+ T cells) and activated them. With more of these cells, tumors grew more slowly in mice that performed exercise training,” says co-corresponding author Dai Fukumura, MD, PhD, deputy director of the Edwin L. Steele Laboratories in the Department of Radiation Oncology at MGH.

As Fukumura and colleagues report in the journal Cancer Immunology Research , the beneficial effects of exercise training are dependent on CD8+ T cells; when the researchers depleted these cells in mice, tumors in mice that exercised no longer grew at a slower rate.

They also found evidence that recruitment of CD8+ T cells to tumors was dependent on two chemical recruiters (chemokines) labeled CXCL9 and CXCL11. Levels of these chemokines were increased in mice that exercised, and mice that were genetically engineered to lack the receptor (docking site) for these chemokines did not recruit CD8+ T cells and did not have an anti-tumor benefit.

“Humans whose tumors have higher levels of CD8+ T cells tend to have a better prognosis, respond better to treatment, and have reduced risk of cancer recurrence compared with patients whose tumors have lower levels of the immune cells, effects that were echoed by a reduced incidence of metastasis, or spread, of the cancers in mice that exercised,” says co-corresponding author Rakesh K. Jain, PhD, director of the Steele Labs at MGH and Andrew Werk Cook Professor of Radiation Oncology at HMS.

CD8+ T cells are also essential for the success of drugs known as immune checkpoint inhibitors, such as Keytruda (pembrolizumab), Opdivo (nivolumab) and Yervoy (ipilimumab), which have revolutionized therapy for many types of cancer, but have to date had only limited success in breast cancer. The researchers found that exercise-trained mice displayed a much better response to immune checkpoint blockade, while the drugs did not work at all in sedentary mice.

“We showed that daily sessions of a moderate-to-vigorous intensity, continuous aerobic exercise training, lasting 30-45 minutes per session, induces a profound reprogramming of the tumor microenvironment that rewires tumor immunity, recruiting and activating CD8+ T cells to an unprecedented level with a non-pharmacological approach. Similar exercise training could be prescribed to a patient referred to an exercise oncology program,” says Igor L. Gomes-Santos, PhD, lead author and exercise physiologist and post-doctoral fellow in the Steele Labs.

He notes that current clinical guidelines focus on general wellness, improved fitness levels and quality of life, but not necessarily on improved cancer treatment, especially immunotherapy, and that this lack of evidence limits its application in clinical practice.

More convincing, mechanism-based data are needed to motivate oncologists to discuss exercise training with their patients, to motivate patients to become more active and to expand implementation of outpatient exercise oncology programs, the investigators say.

###

The work was supported by grants from the National Institutes of Health to Fukumura and Jain as well as the National Foundation for Cancer Research, Harvard Ludwig Cancer Center, Advanced Medical Research Foundation and Jane’s Trust Foundation to Jain and a fellowship from the Sao Paulo Research Foundation (Brazil) for Gomes-Santos.

About the Massachusetts General Hospital

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. In August 2020, Mass General was named #6 in the U.S. News & World Report list of “America’s Best Hospitals.”

Here is another report on exercise and healthy liver

News Release 12-Apr-2021

Exercise promotes healthy living and a healthy liver

Researchers at the University of Tsukuba show that in non-alcoholic fatty liver disease, regimented exercise has beneficial effects on the liver that are unrelated to weight loss, and they reveal the mechanisms underlying these benefits

University of Tsukuba

Research News

Tsukuba, Japan – Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder worldwide, affecting as much as a quarter of humanity. It is characterized by fat accumulation in liver cells and may progress to inflammation, cirrhosis and liver failure. Now, researchers at the University of Tsukuba reveal the positive effects, beyond the expected weight-loss benefit, of exercise on the liver.

NAFLD is associated with unhealthy behaviors such as overeating and a sedentary lifestyle. In Japan 41% of middle-aged men have NAFLD and 25% will progress to non-alcoholic steatohepatitis (NASH) and hepatic dysfunction.

Weight reduction is fundamental to NAFLD management. Unfortunately, achieving a targeted bodyweight without supervision is difficult, and maintaining this over time even more so. Hitherto, exercise was considered adjunctive to dietary restrictions for weight loss but the other benefits such as reduced hepatic steatosis (fatty change) and stiffness are being increasingly recognized. However, the underlying mechanisms remain unclear.

“We compared data from obese Japanese men with NAFLD on a 3-month exercise regimen with those on dietary restriction targeting weight loss,” senior author Professor Junichi Shoda explains. “We tracked hepatic parameters, reduction in adipose tissue, increase in muscle strength, reductions in inflammation and oxidative stress, changes in organokine concentrations, and expression of target genes of Nrf2, an oxidative stress sensor.”

The researchers found that exercise preserved muscle mass better, though with modest decrease of body and fat mass. Remarkably, ultrasound elastography revealed that the exercise regimen reduced liver steatosis by an additional 9.5%, liver stiffness by an additional 6.8%, and the FibroScan-AST Score (a measure of liver fibrosis) by an additional 16.4% over the weight-loss regimen.

Additionally, the exercise regimen altered the circulating concentrations of specific organokines and apparently induced anti-inflammatory and anti-oxidative stress responses through activation of the Nrf2 (nuclear factor E2-related factor 2), an oxidative stress sensor. It also enhanced the phagocytic capacity of Kupffer cells which help maintain liver function.

Professor Shoda explains the relevance of their findings. “Our research shows how exercise prevents liver steatosis and fibrosis in NAFLD and clarifies that this benefit is compounded by preservation of muscle mass and is independent of weight changes. Patients on exercise regimens may become demotivated and drop out if they do not experience significant weight loss. Therefore, moderate to vigorous intensity exercise should be integrated in all NAFLD therapeutic regimens, and patients at risk for NASH should be encouraged to persevere with moderate to high intensity exercise regardless of whether or not they lose weight.”

###

The article, “Weight loss-independent benefits of exercise on liver steatosis and stiffness in Japanese men with NAFLD” was published in JHEP Reports (2021) at DOI: https://doi.org/10.1016/j.jhepr.2021.100253.