Researchers at The University of Texas at Austin and The University of Texas MD Anderson Cancer Center announced on Mar. 17 a discovery that could explain why some chemotherapy drugs not only kill cancer cells directly but also prompt the immune system to attack them.
The finding is significant because it suggests that certain chemotherapy agents might trigger an innate immune response, potentially leading to more effective cancer treatments with lower doses. This could help reduce side effects for patients and improve outcomes by enlisting the body’s own defenses alongside traditional therapies.
The research team tested an experimental chemotherapy agent called Compound 1, which causes a build-up of reactive oxygen species in cancer cells. They found that treated cancer cells released signals similar to those produced by virus-infected cells, a phenomenon known as viral mimicry. When these pretreated cells were injected into preclinical models, the immune system responded as if fighting a viral infection and remained primed to attack future cancer cells, even those not previously exposed to the drug.
“Initially, it didn’t make sense as to why chemotherapies sometimes generated an immune response,” said Brent Iverson, the Warren J. and Viola Mae Raymer Professor of chemistry at UT and co-author of a recent paper describing the work in the Proceedings of the National Academy of Sciences. “Why did the immune system see these cancer cells as not being ‘self’ and attack them? But now we can connect the dots. The cancer cells are acting like they’re infected.”
Jonathan Sessler, R. P. Doherty, Jr. – Welch Regents Chair in Chemistry at UT and developer of Compound 1, said: “What’s most exciting to me is the clinical ramification that maybe you could be using less chemotherapy on patients to have a better outcome, so less might be more.” Matthew Levine, a UT chemistry graduate student who led the research, added: “That might help identify combinations and dosing schedules that better engage the immune system, such as by pairing cytotoxic drugs with immunotherapies in a way that maximizes immune activation while avoiding excessive damage to immune cells themselves.”
The study was supported by grants from the National Institutes of Health (NIH), The Robert A. Welch Foundation, and a collaborative grant between UT Austin and UT MD Anderson Cancer Center. Future work will focus on screening existing chemotherapy drugs for their ability to induce viral mimicry and exploring combinations with immunotherapy.
Levine said: “If our viral mimicry hypothesis is correct, one of the potential breakthroughs of this approach over traditional treatment is that, since this plan harnesses lower dose and primarily relies more on the host immune system, one might not have to treat tumors multiple times… These tumors might have less of a chance to develop resistance to treatment.” He also noted ongoing efforts to seek clinical collaborations for analyzing patient samples treated with chemotherapeutic agents.
This discovery builds on longstanding collaborations between UT Austin and UT MD Anderson Cancer Center. The University of Texas Medical Center is scheduled to open in Austin in 2030 with integrated cancer care through its partnership with MD Anderson.
