Van Andel Institute Researcher Demonstrates Predictive Value of Cell Produced in Tumor Microenvironment
Nasopharyngeal carcinoma (NPC) is uncommon in the United States and most other nations, representing less than 1 case per 100,000 in most populations. The most well-known NPC-patient in the U.S. is perhaps the baseball player Babe Ruth, who died from the disease in 1948. NPC is, however, extremely common in southern China and Southeast Asia, where it accounts for 18% of all cancers in China, and in some regions is 25 times more common than in the U.S.
“These results deepen our understanding of the inflammatory mechanisms involved in NPC progression,” said Chao-Nan Qian, M.D., Ph.D., a researcher with Van Andel Institute and Sun Yat-sen University Cancer Center in Guangzhou, China. “Taken together, our data provide novel evidence that tumor-derived cytokines (small cell-signaling proteins) affect the development of cancer and its prognosis, and they are associated with the expansion of a type of interleukin producing cell within the tumor microenvironment.”
The results of the study, published in October in the Journal of Biological Chemistry, indicate an elevated percentage of the interleukin producing cells, known as Th17 cells, in the NPC tumor microenvironment. The research shows for the first time that microenvironment-derived macrophage inhibitory factor (MIF) promotes the generation and migration of Th17 cells mediated by tumor cells, and the promotion effect of MIF on the generation and recruitment of Th17 cells was mainly dependent on the mTOR pathway and was mediated by MIF-CXCR4 axis.
Most importantly, the expression of MIF in tumor-infiltrating lymphocytes (a type of white blood cell), predicted a favorable clinical outcome in NPC patients.
“Taken together, our findings illustrate that tumor-derived MIF can affect patient prognosis, which might be related to the increase of Th17 cells in the NPC tumor microenvironment,” said Dr. Qian.
The accumulation of a Th17 subset of tumor-infiltrating lymphocytes is a general characteristic in many cancers. The relationship between the percentage of Th17 cells and clinical prognosis differs among cancers. The mechanism responsible for the increasing percentage of such cells in NPC is still unknown, as is their biological function.
The study was carried out under the direction of Dr. Qian, Dr. Jiang Li and Dr. Yi-Xin Zeng by researchers from the State Key Laboratory of Oncology in South China, the Department of Nasopharyngeal Carcinoma and Department of Biotherapy of Sun Yat-sen University Cancer Center in Guangzhou and the Laboratory of Cancer and Developmental Cell Biology at Van Andel Institute in Grand Rapids, Michigan.
Van Andel Institute
Established by Jay and Betty Van Andel in 1996, Van Andel Institute is an independent research organization dedicated to preserving, enhancing and expanding the frontiers of medical science, and to achieving excellence in education by probing fundamental issues of education and the learning process. This is accomplished through the work of over 200 researchers in more than 20 on-site laboratories and in collaborative partnerships that span the globe.