A preclinical study headed by researchers at NYU Langone Health has shown how a protein made by stressed cancer cells helps lung and pancreatic tumors evade the immune system. The study found that new drugs designed to block the action of a protein called lipocalin 2 (LCN2) slowed cancer growth in mice by enabling the immune system to target tumor cells. The drugs made aggressive cancers more vulnerable to immunotherapies, which help the immune system attack cancer cells. The research, headed by Thales Papagiannakopoulos, PhD, associate professor in the department of pathology at the NYU Grossman School of Medicine, and published in Nature (“The integrated stress response promotes immune evasion through lipocalin 2”), centered on a cellular survival pathway called the integrated stress response (ISR), which cells use to endure stressful conditions, such as a lack of nutrients. Cancer cells, with their abnormal, aggressive growth, face a continual threat of starvation, are always stressed, and always have the ISR turned on. The ISR in cancer cells triggers the production of a protein called activating transcription factor 4 (ATF4), which in turn triggers the action of many genes that help cancer cells survive. “The ISR and its master transcriptional effector, ATF4, are emerging as key players that respond to several intrinsic stressors during tumorigenesis and contribute to therapy resistance,” the investigators reported. Their newly reported work shows that ATF4 also instructs the cell to release LCN2 to protect the tumor from the immune system. Co-corresponding author Papagiannakopoulos explained, “Stressed cancer cells…
