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The drugs were administered to a group of twenty-seven patients with advanced pancreatic ductal adenocarcinoma. The patients had in the past undergone chemotherapy.</p> <p>The immune activity in the <a href="https://www.news-medical.net/news/20241114/New-drug-strategy-reverses-resistance-to-immunotherapy-in-pancreatic-cancer.aspx" target="_blank" rel="noopener">microenvironment</a> of patients with this common type of pancreatic cancer is suppressed, which allows the tumor to avoid attacks by the immune system.</p> <p>The cancer attracts cells that suppress immune activity into the tumor, thereby limiting the access of <a href="https://my.clevelandclinic.org/health/body/24630-t-cells#:~:text=T%20cells%20are%20a%20type,immune%20cells%20to%20fight%20infection." target="_blank" rel="noopener">T-cells</a> into this environment. This increases resistance to immunotherapies that can successfully treat cancers like lung cancer and melanoma.</p> <p>The team of researchers was led by <a href="https://profiles.hopkinsmedicine.org/provider/marina-baretti/2708392" target="_blank" rel="noopener">Dr. Marinna Baretti</a> and <a href="https://profiles.hopkinsmedicine.org/provider/nilo-azad/2702983" target="_blank" rel="noopener">Dr. Nilofer Azad</a> who co-leads the <a href="https://www.hopkinsmedicine.org/kimmel-cancer-center/research/cancer-genetics-epigenetics" target="_blank" rel="noopener">Cancer Genetics and Epigenetics Program</a>. The researchers discovered that administering the drug combination resulted in tumor shrinkage, observing that the disease didn’t progress either for roughly 10 months.</p> <p>In particular, they found that entinostat modified the tumor microenvironment by reducing the number of suppressive immune cells and growing proliferation and activation of T-cells in the region. This change in the environment allowed nivolumab to bring in more T-cells to eliminate tumor cells. Entinostat, a histone deacetylase inhibitor, is known to alter patterns of gene expression.</p> <p>They also carried out lab analyzes of tissue and blood samples obtained from the patients, which helped demonstrate how the drugs performed on the microenvironment level.</p> <p>The research is based on findings from two separate studies, one of which was led by <a href="https://profiles.hopkinsmedicine.org/provider/elizabeth-jaffee/2985750" target="_blank" rel="noopener">Dr. Elizabeth Jaffee</a>, Kimmel Cancer Center’s deputy director. The investigators discovered that entinostat could modify suppressive immune cell activity and bring in stronger T cells into the tumors.</p> <p>A separate study also discovered that combining nivolumab and entinostat substantially enhanced survival in mice treated using both drugs, as compared to those that received only one of the drugs.</p> <p>In their report, the researchers noted that their findings could help develop a road map that could be used in future trials for this pancreatic cancer and other <a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC10141036/" target="_blank" rel="noopener">cancers resistant to immunotherapies.</a> They are now focused on understanding how this benefit can be expanded to help even more patients.</p> <p>The study’s findings were reported in <a href="https://www.nature.com/articles/s41467-024-52528-7" target="_blank" rel="noopener">Nature Communications.</a> The study was supported by the National Institutes of Health and the National Cancer Institute, among other institutions.</p> <p>This additional information from this study about how to combat resistance to immunotherapy promises to expand the range of applicability of immunotherapies developed by companies like <a href="https://www.biomedwire.com/clients/scinai-immunotherapeutics-ltd/?symbol=SCNI" target="_blank" rel="noopener">Scinai Immunotherapeutics Ltd. 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