healthmedicinet

In the fight against cancer, researchers from Baylor College of Medicine have identified a key regulator of the immune system’s anti-cancer response. The research, which was published in the Proceedings of the National Academy of Sciences, demonstrates that in animal models of breast and prostate cancer, deleting the gene SRC-3, particularly in a class of immune cells known as regulatory T cells (Tregs), caused a lifelong anti-cancer response that eliminated the tumor without the typical side effects seen with other treatments.n

transmitting Tregs deficient in SRC-3 to animals bearing undesirable side effects. The results recommend conducting more research to assess the effectiveness of this treatment strategy for curing human illness.nn

“More than 30 years ago, my lab discovered a protein we called steroid receptor coactivator (SRC) that is required for the effective regulation of gene activity,” said corresponding author Dr. Bert W. O’Malley, chancellor and professor of molecular and cellular biology at Baylor. “Since then, we have discovered that a family of SRCs (SRC-1, SRC-2 and SR-3), regulates the activity of a variety of cellular functions.”n

Over the years, the O’Malley lab and colleagues have been particularly interested in SRC-3 and its role in cancer. SRC-3 is not only highly expressed in all human cancers and plays a role in cancer growth, but it is also strongly expressed in Tregs that regulate the immune response to cancer. Intrigued by the abundance of SRC-3 in Tregs and suspecting that it might play a role in controlling cancer progression, O’Malley and his colleagues investigated the effect of eliminating the gene SRC-3 in Tregs on breast cancer growth.n

The team generated mice lacking the SRC-3 gene only in Tregs (SRC-3 knock-out) and then compared breast cancer progression in these mice with the progression in mice that had the SRC-3 gene.n

“We were surprised by the results,” O’Malley said. “Breast tumors were eradicated in the SRC-3 knock-outs. A subsequent injection of additional cancer cells in these mice did not give rise to new tumors, showing that there was no need to generate additional SRC-3 knock-outs to sustain tumor resistance. Importantly, transferring these cells to animals carrying pre-established breast tumors also resulted in cancer eradication. We obtained similar results with prostate cancer.”n

The team also discovered that Tregs lacking SRC-3 mediated long-lasting tumor eradication by effectively modifying the environment surrounding the tumor into one that favored its elimination.n

Using a variety of laboratory techniques, O’Malley and his colleagues discovered that the modified Tregs proliferated extensively and preferentially infiltrated breast tumors where they released compounds that generated an anti-tumor natural killer cells—that directly attacked the tumor and, on the other side, modified Tregs blocked other immune cells that attempted to stop the anti-tumor response.n

“Other published treatments seem to reduce cancer therapy.”