Pericytes May Help Some Tumors Evade the Immune System
A study by researchers at Sweden's Karolinska Institutet is reportedly the first to suggest that cells in the tumor blood vessels contribute to a local environment that protects the cancer cells from tumor-killing immune cells. The results, published by Hong et al in the Journal of the National Cancer Institute, may contribute to the development of better immune-based cancer therapies.
Immune-based antitumor therapies have attracted great attention in recent years and achieved large success rates, especially in malignant melanoma. However, many patients still do not respond to immune-based therapies.
The Role of Pericytes
The results from this study imply that tumor pericytes—cells that are part of the tumor blood vessels—critically manipulate the tumor environment, helping the cancer cells escape immune surveillance.
“Understanding the interplay between tumor pericytes, malignant cells, and the immune system might help in designing more personalized and effective therapeutic approaches,” said principal investigator Guillem Genové, PhD, Senior Lecturer in the Department of Medical Biochemistry and Biophysics at Karolinska Institutet.
Tumors evade the immune system by a variety of mechanisms, one being the recruitment of myeloid-derived suppressor cells, which suppress the ability of T cells to destroy cancer cells. It is known that the more myeloid-derived suppressor cells present, the worse the prognosis or therapy response of the patient. Tumors secrete signal molecules such as interleukin-6 (IL-6), which help in recruiting myeloid-derived suppressor cells, but the mechanisms behind IL-6 tumor secretion are unknown.
The researchers found that the higher the number of pericytes, the more “normal” the tumor environments appeared. In contrast, diminished pericyte numbers altered the microenvironment and correlated to higher IL-6 expression from the malignant cells and more myeloid-derived suppressor cells. They also identified a subset of patients with breast cancer who had fewer pericytes and increased myeloid-derived suppressor cells, correlating to a worse prognosis and more aggressive characteristics of the tumor.
“Our work suggests that ways to increase the numbers of pericytes could potentially decrease IL-6 expression. This could improve cytotoxic T-cell activity and result in better antitumor effects,” said Dr. Genové.
Dr. Genové is the corresponding author of the Journal of the National Cancer Institute article.
The research was supported by grants from, among others, the Swedish Cancer Foundation, the Strategic Cancer Research Program (StratCan) and BRECT Breast Cancer Theme Centrum at Karolinska Institutet, and the Swedish Research Council–supported STARGET Linneus Center of Excellence.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
