Potential Biomarker for Kidney Cancer: The Immune System?

Can what’s happening to the immune system in kidney cancer be tracked? Are there biological footprints that might lend themselves to a test? Quite possibly!

Published in Discovery - Winter 2020

There’s no PSA equivalent for detecting or monitoring kidney cancer. Brady investigators, supported by funding from Brady Advisory Board members Patricia and Kevin Kiernan, are hoping to change that.

They have been building an understanding of kidney cancer biomarkers and, in the process, learning much more about the disease. “When we started looking for kidney cancer biomarkers, we thought we would find sugars and proteins in the urine or blood that were released by the cancerous cells,” says urologist Phillip Pierorazio, M.D. “It turns out, we are more likely to detect sugars and proteins that describe the immune system’s response to these kidney tumors. This is because kidney cancers suppress the body’s immune system as they grow and spread.”

Can what’s happening to the immune system in kidney cancer be tracked? Are there biological footprints that might lend themselves to a test?

Quite possibly! The Kidney Cancer Biomarker Group, headed by Pierorazio, examined the urine of 100 patients with either benign tumors, benign-behaving kidney cancer, or aggressive kidney cancer, and found a number of lactose-containing molecules that could differentiate these groups. “Importantly, these lactose- containing molecules were cell-surface antigens – tiny sugar molecules used by the immune system to identify good from bad cells,” says Pierorazio.

Scientist Jelani Zarif, Ph.D., and colleagues evaluated the role of macrophages in the development of early to aggressive forms of kidney cancer. “Macrophages are immune cells that engulf and digest cellular debris, bacteria – and, in some circumstances, cancer cells,” Zarif explains. But certain types of macrophages, called M2, can actually promote cancers by suppressing the immune system around a malignant cell. Zarif’s study, reported in European Urology Oncology, found more macrophages and more immunosuppression in kidney cancer cells than in the normal surrounding kidney tissue.

Scientist Richard Zieran, M.D., Ph.D., and colleagues are evaluating nano-vesicles in the blood and urine of patients with kidney cancer. “Traditionally, researchers thought these were the ‘trash cans’ of cells,” says Zieran. “But we are increasingly finding evidence that these nano-vesicles actually contain valuable information in the form of proteins and nucleic acids. They are a form of communication between cells.” Zieran’s early work, presented at the American Association for Cancer Research’s meeting in Atlanta, suggests that cancer cells may produce more vesicles than healthy cells, and thus influence the tumor environment.

“As we learn more about the immune system, we believe we are getting closer to finding the elusive biomarker that will help us diagnose and guide treatment for many patients with kidney tumors,” says Pierorazio.