Researchers at Moffitt Cancer Center and colleagues at the University of South Florida and Tianjin Medical University Cancer Institute and Hospital in China have discovered that combining chemotherapy drugs and immunotherapy cancer vaccines results in an enhanced anti-tumor effect. The results, achieved by testing cancer cells in a laboratory, are surprising because chemotherapy generally reduces immunity and could cancel out the benefits of immunotherapy when given together.
Their study appears in the Aug. 31 online issue of Cancer Research, a publication of the American Association for Cancer Research.
"Our question of interest for this study was 'Can immunotherapy be used in combination with conventional chemotherapy in patients with advanced cancer?' " said study lead author Dmitry I. Gabrilovich, M.D., Ph.D., senior member of Moffitt's Immunology Program. "The use of conventional cancer chemotherapy in combination with immunotherapy was previously not thought to be appropriate due to the immunosuppresive effects usually associated with chemotherapy. However, we identified a mechanism by which the two therapies could work together."
The mechanism involved was the dramatic upregulation of the mannose-6-phosphate receptor (MPR) to the tumor cell surface. According to the researchers, normally more than 90 percent of total MPR is localized inside the cells, but after chemotherapy, large amounts of MPR localized on the cell membrane.
The researchers attributed this to autophagy.
"Autophagy is a reversible process than can contribute to both tumor cell death and survival," explained Gabrilovich. "When this pathway is initiated, cellular material is sequestered by autophagosome. The mechanism of autophagosome formation depends on the type of chemotherapy used."