Kunz has received honoraria from your Speakers Bureau of Roche Pharma and travel support from Novartis Pharma GmbH and Bristol-Myers Squibb GmbH. Footnotes Publishers Notice: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.. the first cycle of treatment (median MAD 39.2 7.3% vs. 30.5 4.1% and 37.7 4.6 vs. 24.0 6.4). Immune-related adverse events (irAE) were accompanied by a higher percentage of activated CD4+ (CD4+CD38+HLADR+) T cells before the second treatment cycle (median MAD 14.9 3.9% Methylprednisolone vs. 5.3 0.4%). In summary, PBMC immune monitoring of immune-checkpoint inhibition (ICI) treatment in melanoma appears to be a promising approach to identify early markers of treatment response and irAEs. V600E mutation was observed in five patients. In ten patients, at least 2% of tumor cells expressed PD-L1. PD-L1 was unfavorable in four patients (Table 1). Table 1 Clinical characteristics of melanoma patients included in this study. = 0.012) increased over time, starting with a median of 3.3% (time point 1) vs. medians 3.4% (time point 2), Rabbit polyclonal to LRRC15 8.7% (time point 3) and 5.5% (time point 4) (Determine 1D). Open in a separate window Physique 1 PD-1 expression on T cells in stage IV melanoma patients under ICI therapy. PBMC were taken from patients at indicated time points and PD-1 expression on T cells was analyzed by circulation cytometry (FACS). Blood samples were taken immediately before first treatment with anti-PD-1 (either alone or in combination with anti-CTLA-4) (time point 1), immediately after first treatment on the same day (time point 2), after two or three weeks (time point 3) and after three months (time point 4). (A) PD1+CD3+ T cells. (B) PD1+CD4+ T cells. (C) PD1+CD8+ T cells. (D) CD4+CD38+HLADR+ T cells. Nominal (unadjusted) = 15 patients. Two patients, patients 12 and 14 (Table 1), were excluded from the final analyses because of an early switch in treatment regimen to BRAF/MEK-inhibition and unknown cause of death, respectively. Differences between post-first dose levels (time point 2) and levels at the time point of first appearance of irAE were analyzed by Wilcoxon signed-rank test for all patients with observable irAE within the follow-up time. Based on the small sample size of the offered pilot study, the limited statistical power did not allow for statistical confirmation of the observed differences with proper adjustment for multiple screening. Instead, the most prominent differences were selected by a nominal (unadjusted) 0.05. For these features, the median as well as the median complete deviation (MAD) of measured levels are offered for each group (R function MAD with parameter constant = 1). Supplementary Materials The following are available online at https://www.mdpi.com/article/10.3390/ijms22158017/s1. Click here for additional data file.(1.0M, zip) Author Contributions R.R., P.G. and A.B. designed the study, performed the data acquisition and analysis, and contributed to writing and editing of the draft. T.G. supported the data acquisition and analysis and provided study material. U.S., U.K., F.L. and J.-C.S. designed the study, supported data interpretation, and revised the work critically. M.K. (Markus Kreuz) and K.R. did the statistical analysis, supported data interpretation and revised the work critically. M.Z. and M.K. (Manfred Kunz) designed the study, performed the data acquisition and interpretation, and drafted the work. All authors approved the version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All authors have read and agreed to the published version of the manuscript. Funding No institutional funding was received. Institutional Review Table Statement The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the local Methylprednisolone Ethics Committee of the Medical Faculty of the University or college of Leipzig (AZ 130/19-ek). Informed Consent Methylprednisolone Statement Informed consent was obtained from all subjects involved.