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Introduction Despite encouraging phase I and II study results, vaccination of ovarian cancer patients with abagovomab – an anti-idiotypic mAb that mimics the ovarian cancer CA125 protein – failed to demonstrate efficacy in the phase III trial named MIMOSA (NCT00418574). We postulated that in this trial patients with a more robust immune system did respond to abagovomab but went undetected among a larger number of non-responders. We also postulated that assessment of the immune system status ahead of abagovomab administration might predict patients’ propensity to respond to abagovomab. Materials and methods The immune system status was assessed as percentage and absolute count of CD8 + T cells producing IFN-γ after stimulation with Staphylococcal Enterotoxin B (SEB) in 80 patients on abagovomab and 31 patients on placebo from the MIMOSA trial ahead of treatment. Optimal cutoffs of the two variables were calculated by the web application “Cutoff Finder” as the points with most significant (log-rank test) splits based on relapse-free survival (RFS). The Kaplan–Meier curves and log-rank test served to estimate and compare RFS in patients with percentage and absolute count of IFN-γ producing CD8 + T cells around the cutoffs. Results Patients on abagovomab with IFN-γ producing CD8 + T cell percentage above the cutoff had a better RFS (p = 0.042) than those with IFN-γ producing CD8 + T cell percentage below the cutoff. Patients on abagovomab with IFN-γ producing CD8 + T cell absolute count above the cutoff had a better RFS (p = 0.019) than those with IFN-γ producing CD8 + T cell absolute counts below the cutoff. Consistently, the RFS of patients on abagovomab with IFN-γ producing CD8 + T cell percentage and absolute counts values below the respective cutoffs was identical to that of patients on placebo. Neither the percentage nor the absolute count of IFN-γ producing CD8 + T cells correlated with RFS in patients on placebo. Conclusions A robust immune system is essential to obtain a clinical response in OC patients undergoing abagovomab immunotherapy whereas a robust immune system does not confer per se a survival advantage. Further work will clarify whether the results shown here apply only in the present setting or extend to other types of cancer and/or immunotherapeutic agents. [ABSTRACT FROM AUTHOR]

Simple Summary: PD-1/PD-L1 axis blockade immunotherapy leverages on assessment of tumour PD-L1 status by immunohistochemistry for identifying cancer patients' who would benefit most from this therapy. Because some PD-L1 negative cancer patients also benefit from the treatment, it has been postulated that spatial heterogeneity of PD-L1 expression in tumour tissue may reduce the predictive value of the test. Here we demonstrate for the first time the presence of PD-L1+ circulating tumor–derived microvesicles in the blood stream of high grade serous ovarian cancer patients and propose the assessment of tumor-derived circulating PD-L1+ microvesicles to be inserted in predictive algorithms for complementing tumour PD-L1 status. Background: Ovarian cancer (OC) has recently attracted attention for the use of PD-1/PD-L1 axis blocking agents, with durable activity reported only in a subset of patients. The most used biomarker for sensitivity to the PD-1/PD-L1 axis blockade is tumour PD-L1 status by immunohistochemistry. However, patient stratification using this method suffers from intrinsic heterogeneity of OC, likely contributing to the unsatisfactory results obtained so far. Cells communicate with each other by releasing microvesicles (MVs) that carry parental cell surface features. Thus, we hypothesised that PD-L1+ tumour cells (TC) and infiltrating PD-L1+ leukocytes should shed MVs carrying surface PD-L1 that may serve as a proxy for the whole tumour PD-L1 status. Results: We showed for the first time the presence of measurable amounts of TC- and leukocyte-derived PD-L1+ MVs (range: 1.4–178.8 MVs/μL and 6.2–504.8 MVs/μL, respectively) in the plasma of high-grade serous OC (HGSOC) patients (n = 63), using a sensitive flow cytometry platform. The concentration of PD-L1+ MVs of either origin did not associate with the PD-L1 status of TCs and leukocytes in the tumour biopsies, suggesting that the circulating PD-L1+ MVs also included ones from locations not selected for immunohistochemistry analysis and represented the PD-L1 status of the whole tumour mass. In this study, we also describe the serendipitous discovery of circulating PD-L1+ MVs of platelet origin (10.3–2409.6 MVs/μL). Conclusions: The enumeration of circulating PD-L1+ MVs in HGSOC patients may provide a novel direction for assessing the tumour PD-L1 status and contribute to HGSOC patient stratification for immunotherapy interventions. The presence of circulating PD-L1+ MVs of platelet origin, a finding not yet reported in HGSOC patients, warrants further studies. [ABSTRACT FROM AUTHOR]

The original version of this article unfortunately contained a mistake. [ABSTRACT FROM AUTHOR]