An autoimmune side effect of immune checkpoint inhibitors (ICI) drugs could signal improved kidney cancer control, according to a new study by researchers at UT Southwestern’s Kidney Cancer Program (KCP).
Today in the Journal of Immunotherapy for Cancercan have far-reaching effects on patients treated with ICIs, a type of immunotherapy used for a large number of cancers, including the lung, breast, liver, and cervix.
Renal cell carcinoma, the most common type of kidney cancer, is the ninth leading cause of cancer in the United States. Once the cancer has spread or metastasized to other organs, the five-year survival rate averages 12 percent.
With the advent of ICIs, kidney cancer survival rates are improving. However, only a fraction of patients respond to ICIs – and whoever reacts to them is unpredictable. ICIs deactivate the camouflage mechanisms established by tumors in order to avoid being killed by immune cells. However, turning off these cloaking mechanisms also increases the likelihood that the immune system will turn against the body and cause autoimmune side effects.
KCP researchers believe that kidney cancer patients whose immune systems have attacked their kidneys may be more likely to benefit from ICIs. Using Kidney Cancer Explorer, a proprietary tool that extracts information from electronic health records, researchers identified patients with metastatic kidney cancer who were treated with ICIs between 2014 and 2018. Using this tool, they analyzed thousands of laboratory test results to identify patients whose kidney function was compromised. They found 36 such patients out of 177 patients.
In three of the 36 patients, the impairment was due to an immune-mediated attack. A fourth recent patient was also identified. All four patients developed acute interstitial nephritis (AIN), an autoimmune disease in which immune cells attack kidney cells, causing inflammation and swelling. While ICIs cause reactions to cancer in up to 40 percent of patients, in this case all four patients reacted with AIN.
“Response is very important for 100 percent of patients,” says Dr. Roy Elias, assistant instructor for internal medicine and co-lead author of the study. “If a patient develops AIN, it is a sign that the treatment may be working.”
This is not the first time a certain autoimmune effect has been linked to an increased response rate to ICIs, says Dr. James Brugarolas, Professor of Internal Medicine and Director of the Kidney Cancer Program. In fact, patients with melanoma who developed vitiligo, a condition in which skin pigment cells are killed by immune cells, were also more likely to respond.
After identifying a second example of an immune attack on the tissue of origin associated with a favorable cancer response, the KCP researchers suggest that this finding may be generalizable to other tumor types.
“All cancer cells start out as normal cells,” says Brugarolas. “Even after becoming vicious, they retain some of their original characteristics. Therefore, an attack on the original tissue can signal a higher probability that the immune system will also recognize and attack the cancer. ”
Further study will be needed to determine whether positive results are generalizable to patients with other cancers who experience similar immune attacks against the cell of origin of the cancer.
UT Southwestern Medical Center
Patel, V., et al. (2020) Acute Interstitial Nephritis, a Potential Predictor of Response to Immune Checkpoint Inhibitors in Renal Cell Carcinoma. Journal of Cancer Immunotherapy. doi.org/10.1136/jitc-2020-001198.
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