Under normal circumstances, the immune system recognizes and successfully fights cancer cells, eliminating them as they develop, but sometimes the process breaks down and tumors form. A new study explains why.
When cancer cells block the function of a gene called NLRC5, they can evade the immune system and proliferate.
“We now know why cancer cells can escape from our immune system,” says Koichi Kobayashi, the study’s lead author and a professor at the Texas A&M College of Medicine.
NLRC5 regulates genes that code for molecules on the surface of cells that present fragments of foreign proteins—such as those from a virus or bacterium—that have invaded the cell. These fragments notify a part of the immune system called cytotoxic T cells, triggering an immediate response from the immune system against that particular foreign antigen.
The new study shows that the same system should work to destroy cancer cells, but sometimes the cells find a way to disable the NLRC5 gene and form tumors.
“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,” says Sayuri Yoshihama, first author of the PNAS study and a fellow in Kobayashi’s lab.
Based on biopsy samples from 7,747 solid cancer patients in the Cancer Genome Atlas (TCGA) database, expression of this NLRC5 gene is highly correlated with cancer patient survival in various cancer types—especially melanoma, rectal cancer, bladder cancer, cervical cancer, and head/neck cancer—with patients who survive longer tending to have greater expression of NLRC5.
Among these, melanoma and bladder cancer displayed the most striking differences, with 5-year survival rates of 36 percent and 34 percent in the NLRC5-low expression group compared with 71 percent and 62 percent in the NLRC5-high expression group, 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,” says Kobayashi.
It might be especially relevant for melanoma patients, both because NLRC5 mutation rate is relatively high and because its levels of expression are highly predictive of survival for that cancer type.
The team has filed a provisional patent application to develop and validate a test that can, based on NLRC5 expression levels, predict cancer patient survival and therapeutic response. The hope is that the test will give health care providers one more tool for determining the best treatment strategy for cancer patients to eliminate the burden of costly, unhelpful therapies.
Eventually, Kobayashi and his team hope this discovery might also lead to new therapeutic strategies for cancer.
“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,” says Kobayashi.
Still, he advises caution. This mechanism of evading the immune system is not employed by every cancer cell, and the research still needs to be replicated in an animal model.
The research was conducted in collaboration with Margaret Shipp at the Dana-Farber Cancer Institute in Boston and Gregory Lizee at the MD Anderson Cancer Center in Houston.
Source: Texas A&M University