Presurgical neoadjuvant chemotherapy (NACT) altered the immune microenvironment in patients with stage IIIC/IV tubo-ovarian high-grade serous carcinoma (HGSC), perhaps enhancing the potential response to immunotherapy, investigators report.
“The results suggest that the effects of immunotherapy might be enhanced if given after chemotherapy, potentially improving disease control in patients with advanced HGSC and other cancer types,” wrote Dr. Steffen Bohm of Barts Cancer Institute in London and his associates (CCR. 2016. doi: 10.1158/1078-0432.CCR-15-2657).
Dr. Bohm and associates collected pre- and postchemotherapy biopsies and blood samples from 60 patients with stage IIIC or IV HGSC; 54 patients underwent platinum-based neoadjuvant chemotherapy and 6 received chemotherapy after debulking surgery. The investigators used immunohistochemistry and RNA sequencing to evaluate the changes before and after chemotherapy. The patients were grouped by their response to chemotherapy.
Results indicated that NACT induced T cell activation, with results most pronounced among those who had a good response to chemotherapy. Among a subset of 25 patients, omental metastases biopsies indicated CD8+ T cells and memory cells were present in the tumors after NACT. Proinflammatory cytokines decreased in all patients following NACT.
Immunohistochemical staining for PD-1 ligands showed that PD-L1 levels were significantly increased in post-NACT samples regardless of a patient’s response to chemotherapy.
“Our results suggest that NACT opens a window of opportunity for immunotherapies such as immune checkpoint blockade for patients with different levels of response to chemotherapy,” Dr. Bohm and associates said.
The study was funded by the Swiss Cancer League, the European Research Council, Cancer Research UK, and Barts and The London Charity. The authors had no relevant disclosures to report.
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