Yervoy (ipilimumab) alone doesn’t help treat advanced prostate cancer patients. Yervoy activates the immune system by going after the CTLA-4 protein receptor that slows immune-system activity. But prostate cancer responds to Yervoy by increasing two other immune checkpoint molecules, PD-L1 and VISTA.

And both send a don’t-eat-me signal to immune cells. That reaction is why Yerboy, by itself, doesn’t help.

However, Yervoy combined with PD-1 and VISTA inhibitors might be a good was to treat advanced prostate cancer.  A study called, “VISTA is an inhibitory immune checkpoint that is increased after ipilimumab therapy in patients with prostate cancer,” was published in Nature Medicine.

“This paper highlights the importance of studying immune response longitudinally,” lead author Padmanee Sharma, MD, PhD, said in a press release.

“Observing immune response at one point in time doesn’t reflect what’s going on because the immune system is so dynamic,” said Sharma, a professor of genitourinary medical oncology and immunology at the University of Texas MD Anderson Cancer Center. “So baseline sampling in prostate tumors shows minimal immune infiltrate. You can change that with ipilimumab, but what else changes becomes incredibly important.”

Prostate cancers have low numbers of T-cells, a kind of white blood cell that can recognize and kill cancer cells.

“We’ve known that prostate cancer is immunologically cold, or quiet, with very little penetration of the tumors or their surrounding microenvironment by immune cells,” Sharma said.

 “Understanding these changes using post-treatment or on-treatment biopsies is important to develop rational combination strategies for these immune-modulating drugs,” Sharma said. “The presurgical clinical trials, also called window of opportunity trials, allow researchers to learn a lot from a small number of patients to guide the design of larger trials.”

The findings suggest that Yervoy could work in synergy with molecules that block the PD-1 and VISTA immune checkpoints. While it brings T-cells toward the tumors, the other drugs could remove the brakes that prevent immune cells from attacking the tumors.