Stopping the Growth of Bladder Cancer by Activating the Immune System

An epigenetics drug currently being used for the treatment of blood cancers and rare sarcomas can stop the growth of bladder cancer by activating the immune system, reports a new study done in mice.

“We’ve discovered for the first time that the drug actually works by activating the immune system, not just by inhibiting the tumor,” said lead study author Dr. Joshua Meeks.

“We think the specific mutations that may make the drug successful are found in almost 70% of bladder cancers,” said Meeks, also a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

Meeks said: “This is the first application of epigenetic therapy in bladder cancer.”

Northwestern investigators showed that the medication, which targets the EZH2 gene abundant in most tumors, can stop the growth of bladder cancer.

When scientists knocked out EZH2 in bladder cancers in mice, the tumors were much smaller and packed with immune cells.

“That was our clue that the immune system may be suppressed by EZH2,” Meeks said. “Next, we gave a commercially available drug (tazemetostat) to inhibit the activity of this gene. It caused a lot of immune cells to pack the bladder. Finally, when we used mice with no T cells, we found the drug was ineffective, confirming that the immune system was likely the primary pathway by which the drug works.

“We find that the treatment is potent immunotherapy in translational research. The drug changes the tumor to prime the immune system, activating CD4 helper cells that coordinate the immune response and recruit more T cells.”

Sources:

Andrea Piunti, Khyati Meghani, Yanni Yu, A. Gordon Robertson, Joseph R. Podojil, Kimberly A. McLaughlin, Zonghao You, Damiano Fantini, MingYi Chiang, Yi Luo, Lu Wang, Nathan Heyen, Jun Qian, Stephen D. Miller, Ali Shilatifard, Joshua J. Meeks. Immune activation is essential for the antitumor activity of EZH2 inhibition in urothelial carcinoma. Science Advances, 2022; 8 (40) DOI: 10.1126/sciadv.abo8043

Northwestern University. “Novel treatment effective for bladder cancer, study in mice shows: Treatment activates the immune system to attack tumor cells.” ScienceDaily. ScienceDaily, 5 October 2022. <www.sciencedaily.com/releases/2022/10/221005141743.htm>.

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