Researchers have discovered why cancer cells are able to cloak themselves from the body’s immune system, allowing them to metastasize and spread throughout the body.

Cancer cells.
Image credits National Cancer Institute.

Cancer is a terrible disease. Contrary to common-held beliefs, however, it’s not a modern disease, nor is it a human-only one. It arises from genetic defects in cells’ DNA. As the tumors develop, more and more mutations are added to the cells’ genetic code.

University of British Columbia scientists have discovered that through this process, cancerous cells lose the proteic pathway used to synthesize interleukein-33. IL-33 is an intermediary in a “warning flag” complex of proteins known as the major histocompatibility complex (MHC.)

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MHC proteins coat diseased or malfunctioning cells so that white blood cells know to swoop in and recycle them — so, when the IL-33 protein disappears, malignant cells look like their ordinary, healthy counterparts to our immune system. Unattacked, they grow and spread out through the body — a step known as metastasis.

“The immune system is efficient at identifying and halting the emergence and spread of primary tumours but when metastatic tumours appear, the immune system is no longer able to recognize the cancer cells and stop them,” said Wilfred Jefferies, senior author of the study working in the Michael Smith Laboratories and a professor of Medical Genetics and Microbiology and Immunology at UBC.

The team found that IL-33 loss occurs in epithelial carcinomas — cancers of organ-lining tissues. This includes prostate, kidney, breast, lung, uterine, cervical, pancreatic, and skin — among many other — types of cancer. With help from the Vancouver Prostate Centre, they studied several hundred patients and found that people suffering from prostate or kidney cancers whose tumours didn’t produce any IL-33 had more rapid recurrence of the condition over a five-year period.

When treating metastatic cancers with the protein, the patients’ immune systems jump-started and began attacking the malignant cells. The group hopes that reversing the genetic processes which rids cancers of marker proteins such as IL-33 will make them visible as targets to white blood cells again.

“IL-33 could be among the first immune biomarkers for prostate cancer and, in the near future, we are planning to examine this in a larger sample size of patients,” said Iryna Saranchova, a PhD student in the department of microbiology and immunology and first author on the study.

Researchers have been desperately searching for an effective cure for cancer, with some success (see here and here). But finding a way to make our own immune system attack tumours would definitely revolutionize how we think about this disease in the future.

The full paper “Discovery of a Metastatic Immune Escape Mechanism Initiated by the Loss of Expression of the Tumour Biomarker Interleukin-33” has been published in the journal Scientific Reports.