how does stress modify tumor-host interactions?

Dr. He’s goal is to understand how chronic mental stress influences the growth of both primary and metastatic colorectal tumors. Specifically, her lab is focused on understanding how stress changes the “soil” of the tumor, known as the “tumor microenvironment.” Cancer patients experience intense stress and epidemiological studies strongly support a link between stress and an increased risk of metastasis and poor survival in cancer patients. Therefore, if we can understand how stress causes cancer progression then we can develop preventive therapies to block the harmful effects of stress. Both clinical and experimental studies reveal that stress can trigger or worsen inflammatory bowel disease (IBD), a chronic gut disorder and a major risk factor for colorectal cancer (CRC). When stress occurs, it can also break down the protective barrier in the intestines and lead to persistent inflammation, causing damage to DNA and creating mutations that can contribute to the development of cancer.

Dr He has already shown that stress hormones activate a type of white blood cells called neutrophils, which transform the environment in the lungs when stressed, making it more favorable for cancer. Stress causes neutrophils to form neutrophil extracellular traps (NETs), which are meshes of DNA from neutrophils with enzymes and proteinases. Normally, NETs are released to fight off infections, but in the case of cancer, they can be “hijacked” to help cancer cells spread. By targeting NETs in lung cancer, the spread of cancer caused by stress can be significantly reduced. This opens up a new potential opportunity for the treatment of stressed cancer patients, and Dr. He wishes to investigate this interaction in colorectal cancer (CRC). Dr. He will focus on how stress-induced NETs in the leaky gut (a gut that allows substances to pass through easily) control the balance of the gut and the development of tumors by combining already validated mouse models for stress and colitis and tissue regeneration. She will study how NETs, the gut epithelium cells, and the immune system interact under stress and then will further apply her stress model to mice with colorectal cancer to track changes caused by NETs in the gut’s immune microenvironment in stressed mice. She hopes to show that targeting NETs alongside immune checkpoint blockade therapy will give better results. With her research, Dr. He hopes discover ways to lessen the negative impact of stress on cancer development and identify molecules that can be targeted for better treatments.