Neo-Adjuvant Chemotherapy Reduces, and Surgery Increases Immunosuppression in First-Line Treatment for Ovarian Cancer

SIMPLE SUMMARY: The immune system plays an important role in the development and progression of cancer. The current treatments for ovarian cancer (surgery and chemotherapy) create changes in the immune system, but it is not clear how. Nevertheless, if immunotherapy is associated on top of this, then it seems crucial to understand what is changing in the current state of the art. In this study, we measured immune-related proteins in the serum of ovarian cancer patients throughout their treatment. We discovered that carboplatin–paclitaxel as a chemotherapeutic treatment reduces immunosuppression and promotes immunostimulation, meaning that the immune system be-comes less hostile and more in favour of the patient. Therefore, chemotherapy seems to induce a temporary window of opportunity to insert immunotherapy during the current treatment of ovarian cancer patients. ABSTRACT: In monotherapy, immunotherapy has a poor success rate in ovarian cancer. Upgrading to a successful combinatorial immunotherapy treatment implies knowledge of the immune changes that are induced by chemotherapy and surgery. Methodology: Patients with a new ovarian cancer diagnosis underwent longitudinal blood samples at different time points during primary treatment. Results.: Ninety patients were included in the study (33% primary debulking surgery (PDS) with adjuvant chemotherapy (ACT), 61% neo-adjuvant chemotherapy (NACT) with interval debulking surgery (IDS), and 6% debulking surgery only). Reductions in immunosuppression were observed after NACT, but surgery reverted this effect. The immune-related proteins showed a pronounced decrease in immune stimulation and immunosuppression when primary treatment was completed. NACT with IDS leads to a transient amelioration of the immune microenvironment compared to PDS with ACT. Conclusion: The implementation of immunotherapy in the primary treatment schedule of ovarian cancer cannot be induced blindly. Carboplatin–paclitaxel seems to ameliorate the hostile immune microenvironment in ovarian cancer, which is less pronounced at the end of primary treatment. This prospective study during primary therapy for ovarian cancer that also looks at the evolution of immune-related proteins provides us with an insight into the temporary windows of opportunity in which to introduce immunotherapy during primary treatment.