Why can the immune system recognize and attack primary tumors but not metastatic tumors? Researchers from the University of British Columbia, in collaboration with the Vancouver Prostate Centre, have the answer.
According to results from a study of human cancer patients, some individuals with prostate or renal cancer tumors showed an exceptional loss of an immune protein called interleukin-33 (IL-33). Without IL-33, cancer cells were able to “hide” from the immune system, and these patients were more likely to see their cancer return within five years.
After further investigating the role of IL-33 in immune evasion by cancer cells, researchers saw that effector T lymphocytes responsible for targeting tumors, like cytotoxic T cells, rely on IL-33 as a signal for denoting if a cell is cancerous. "IL-33 could be among the first immune biomarkers for prostate cancer and we are planning to examine this in a larger sample size of patients," said first author Iryna Saranchova.
The loss of IL-33 occurs in epithelial carcinomas, the cancers that initially develop in the lining of organs: prostate, kidney, breast, lung uterine, cervical, pancreatic, skin, and many more. Compared to other interleukins in the same family, IL-33 has unique intracellular and extracellular features. Inside the cell, IL-33 helps maintain barrier function by regulating gene expression, and outside the cell IL-33 is in charge of immune defense and repair mechanisms while simultaneously triggering the differentiation of helper T cells during the adaptive immune response.
IL-33 also works through a protein complex called major histocompatibility complex (MHC) to alert circulating effector T lymphocytes to the presence of a cancer cell. In addition to signaling the presence of cancer, MHC binds peptide fragments derived from pathogens for display on the cell surface so T cells will be aware of a microbial invasion. Even if MHC is present and functioning, without IL-33, the signaling process is ineffective.
For cancer patients with epithelial carcinomas, monitoring levels of IL-33 could be an effective way to track the progression of their cancer. Additionally, resupplying cancerous cells with IL-33 could help the immune system start to recognize and attack again, according to results from the study. More experiments will be conducted to confirm the efficacy and safety of this treatment in clinical trials.
The present study was recently published in the journal Scientific Reports
Sources: The University of British Columbia
, Nature Immunology
, Immunobiology: The Immune System in Health and Disease 5th edition
, Journal of Cellular Physiology