Administering immunotherapy immediately after chemotherapy may improve response when treating patients with stage IIIC-IV tubo-ovarian high-grade serous carcinoma, according to findings from a study published in Clinical Cancer Research.
While a promising new avenue of cancer treatment, much about how to adequately utilize immunotherapies still remains a mystery. Therefore, researchers conducted a study assessing the effect of neoadjuvant chemotherapy (NACT) on immune activation in certain patients with ovarian cancer and its relationship to treatment response.
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To do so, they obtained pre- and post-treatment omental biopsies and blood samples from 54 patients undergoing platinum-based NACT and 6 patients undergoing primary debulking surgery. All patients were receiving treatment for stage IIIC-IV tubo-ovarian high-grade serous carcinoma.
Tissue samples showed that women who were administered immunotherapy immediately after chemotherapy experienced increased activation of T cells within tumors. That activity was greatest in patients who responded well to NACT. The CD8+ T-cell and CD45RO+ memory cell density in the tumor microenvironment was unchanged after NACT, but biopsies showing a good therapeutic response had significantly fewer FoxP3+ T regulatory (Treg) cells, a finding supported by a reduction in Treg cell gene signature in post- verses pre-NACT samples that were pronounced good responders. Plasma levels of proinflammatory cytokines also decreased in all patients after NACT.
However, increased levels of programmed ligand death 1, a protein that helps cancerous cells evade the body’s immune system, also accompanied these potential benefits.
Thus, researchers concluded that immunotherapy immediately following NACT may improve response in patients with stage IIIC-IV tubo-ovarian high-grade serous carcinoma, but that the effect is tempered by increased levels of PD-L1. Immunotherapeutic agents that target the PD-L1 pathway could therefore be used to further improve response.
"Our study suggests that to give patients the best results not only do the immunotherapy drugs need to be given straight after chemotherapy but they also have to be able to block PD-L1,” explained Frances Balkwill, the Barts Cancer Institute at Queen Mary University of London, England, and senior author of the study. “Clinical trials are now needed to test this theory. This same approach could also be extended to other kinds of cancer where the same types of chemotherapy are used, such as lung cancer."
