NLRC5 Expression Could Determine Cancer Survival, Treatment Response

Certain cancer cells evade the immune system through blocking NLRC5.

In a recent study, researchers found that when cancer cells block the function of the NLRC5 gene, the cells can bypass the immune system and create tumors.

The findings, published in the Proceedings of the National Academy of Sciences, indicate that NLRC5 is a biomarker for cancer survival and therapeutic response.

"We found the major mechanism of how cancer cells escape from our immune system and form tumors," said lead author, said Koichi Kobayashi, MD, PhD. "Cancer cells are born because of genetic changes, such as mutations or rearrangement of pieces of different chromosomes. Because of this, all cancer cells have new, 'foreign' genes, which host T-cells generally detect as tumor antigens. This anti-tumor system works very well."

Previous research indicated that NLRC5 controls major histocompatibility complex (MHC) class I genes, which code for molecules on the cell surface that present fragments of foreign proteins invading the cell, according to the study. The fragments then alert cytotoxic T cells that trigger an immune system response against the foreign antigen.

"If MHC class I antigen presentation does not work, cancer cells will not be killed by T cells," said first author of the study Sayuri Yoshihama, MD, PhD. "We found that function and expression of NLRC5 is reduced in cancer cells by various mechanisms, and the result is immune evasion by cancer cells."

Biopsy samples from 7747 patients with solid cancer were analyzed and researchers found the expression of NLRC5 is highly correlated with cancer survival. Patients with a higher expression tended to live longer.

Researchers found that melanoma and bladder cancer had 5-year survival rates of 36% and 34%, respectively, in the NLRC5-low expression group. In the NLRC5-high expression group, the 5-year survival rates were 71% and 62%, respectively.

"With this finding of NLRC5 as an important biomarker for cancer, we can ultimately predict how long cancer patients can survive and how well cancer treatments might work for them," Dr Kobayashi said.

Researchers said they plan to continue to study the role of NLRC5 in cancer, and plan to develop a test than can predict cancer patient survival and therapeutic response, according to the study.

"If we can regulate the activation of NLRC5 or its expression level, that could be a novel cancer treatment," Dr Kobayashi said. "We hope that in several years, our research may identify potential drug candidates that can increase the levels of NLRC5 and thus help our own immune systems better fight the cancer."

However, researchers caution that this method is not used by every cancer cell and more studies need to be conducted.

"We now know why cancer cells can escape from our immune system," concluded Dr Kobayashi. "No other mechanism is as dramatic as we found. We envision the NLRC5 biomarker as allowing physicians to evaluate and determine the best treatment strategy for each cancer patient, thus leading to better therapeutic outcomes for the more than 12 million people diagnosed with cancer each year."