Chemoimmunotherapy Assures Better Outcomes in Ovarian Cancer
Surabhi Dangi-Garimella, PhD
According to research published in the journal Clinical Cancer Research, immunotherapy right after chemotherapy can piggy back on the immune modifications caused by the chemotherapy, to improve patient response to treatment.
The study assessed the effect of neoadjuvant chemotherapy (NACT) on immune activation in advanced stage, high-grade serous carcinomas. Blood and tissue samples, from 54 patients undergoing platinum-based NACT prior to surgery and 6 undergoing surgery without chemotherapy, were obtained pre and posttreatment. The samples were analyzed for T-cell density and phenotype, and for markers of inflammation by immunohistochemistry and RNA sequencing. Patients were classified as good and poor responders based on a chemotherapy response score that correlates with progression-free survival and overall survival.
Analysis of the tissue samples discovered T-cell activation in samples after NACT, and the activation had a significant correlation with a good response to NACT. Biopsy samples that showed a good response to chemotherapy also had fewer T regulatory cells. Additionally, the authors report that the plasma levels of proinflammatory cytokines decreased in all patients after NACT; also a high proportion of T cells in biopsies expressed immune checkpoint molecules programmed death 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and programmed death ligand 1 (PD-L1) levels were significantly increased after NACT.
“Although we found that chemotherapy activated the T cells, the levels of the protein PD-L1 remained the same or increased. However, immune checkpoint blockade therapies can stop this from happening, so we suggest that immune checkpoint blockade might be a suitable form of immunotherapy to give to ovarian cancer patients after chemotherapy,” said Frances R. Balkwill, PhD, senior author of the study, in a statement. Balkwill is professor of cancer biology at Barts Cancer Institute in Queen Mary University of London, United Kingdom.
“The chemotherapies, carboplatin and paclitaxel, given in our study are also used to treat many different cancer types. It will, therefore, be very interesting and potentially promising if similar effects are seen in other cancer types, such as lung cancer,” Balkwill added.
Böhm S, Montfort A, Pearce O, et al. Neoadjuvant chemotherapy modulates the immune microenvironment in metastases of tubo-ovarian high-grade serous carcinoma. Clin Cancer Res. 2016;22;3025. doi:10.1158/1078-0432.CCR-15-2657.