NEW Ajou Medical Researchers Uncover a Chemical Shield that Protects Tumor Cells
A team of researchers led by those affiliated with the Ajou School of Medicine has demonstrated the existence of a chemical shield that protects tumor cells against attacks by immune cells, revealing a pathway to a new potential tumor treatment strategy.
The team, led by Prof. Park Tae-jun (Dept. of Biochemistry and Molecular Biology), Prof. Kim Jang-hee (Dept. of Pathology), and Prof. Choi Yong-won (Dept. of Oncology-Hematology), has found that senescent tumor cells found in colorectal cancer serve to prevent immune cells from infiltrating the tumor, rendering them ineffective and thereby promoting the progression of colorectal cancer. The team’s findings were published in a paper entitled “Senescent Tumor Cells Build a Cytokine Shield in Colorectal Cancer” in the January 4 issue of Advanced Science.
Senescent cells no longer grow and multiply, but still secrete a variety of substances. Micro-environmental changes associated with diverse illnesses have been attributed to the strong metabolic activities of these senescent cells. Until now, however, little had been known about how these old cells affect cancerous growths.
Having verified the presence of senescent tumor cells in a surgically extracted specimen of colorectal cancer, the Ajou researchers observed that, the greater the number of senescent tumor cells found in a specimen, the slower the penetration of cytotoxic T-cells. The researchers also assayed the secretions found on the surfaces of senescent tumor cells and identified two specific cytokines responsible for the function of immune cells.
The researchers demonstrated that CXCL12, a chemokine, inhibits the infiltration of cytotoxic T-cells into tumor cells, while CSF1, a cytokine, catalyzes the differentiation of macrophages that induce this immunosuppressant effect, thereby undermining the functioning of cytotoxic T-cells. They also found that, by inhibiting CXCL12 alone in mice with colorectal cancer, cytotoxic T-cells infiltrate the tumor cells far better, significantly inhibiting tumor growth.
Concluding that senescent tumor cells in colorectal cancer can affect the progression of the cancer, the researchers expressed hope that their findings will “aid research and lead to the development of a new treatment strategy for colorectal cancer, which is quite resistant to immunotherapy, by targeting senescent tumor cells or the secretions they produce to inhibit immunotherapy.”
This study was made possible with the support of the University-Centered Research Lab Support Program and Basic Research Program of the Ministry of Education, the National Research Foundation of Korea (NRF), and the Bio and Medical Technology Development Program (for the Enhancement of Clinician Scientists’ Research Capabilities) of the Ministry of Science and ICT and the NRF.
Immunosuppressant function of senescent tumor cells in colorectal cancer
# Pictured from left to right: Prof. Park Tae-jun (Dept. of Biochemistry and Molecular Biology), Prof. Kim Jang-hee (Dept. of Pathology), and Prof. Choi Yong-won (Dept. of Oncology-Hematology).