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- W3032061859 abstract "3045 Background: Although anti-PD-1/PD-L1 therapy has become one of the standard treatments for advanced cancers, its low treatment efficacy (10-30%) has remained a major issue. We sought to perform a detailed immune profiling of cells and soluble proteins in order to characterize key regulators and signaling molecules and identify therapeutic targets and biomarkers that may improve treatment efficacy and diagnosis. Methods: This observational study enrolled 49 advanced cancer patients treated with PD-1/PD-L1 blockade monotherapy. Treatment response was assessed by RECIST 1.1. PBMC and plasma samples were collected at baseline and every 6 weeks following initial treatment. Immune profiling of PBMC was done by multi-parametric flow cytometer, and t-SNE analysis was used to identify key immune subtypes. Soluble proteins were evaluated by LUMINEX assays. Cut-off values were determined by ROC curve analysis. Results: Three unique subtypes of immune cells were identified. The population of CD11c + HLA-DR low CD80 + CD86 − CD274 + cells (regDC) at baseline was significantly higher in patients with progressive disease (PD, n=28) than in patients showing clinical benefit (non-PD, n=21; p=0.030). The higher regDC population also correlated with higher levels of IL-8, IL-10, CXCL1, CXCL5, and CXCL11 in plasma. The population of CD4 + CD25 + CD62L + T cells (Treg) was also higher in PD patients (p<0.001). A unique subtype of CD4 + CD28 − T cell, however, was higher in non-PD patients (p<0.001). For the soluble proteins, the levels of sLAG-3 and sGITR in plasma correlated with better clinical outcome in low regDC patients (p=0.004 and 0.044, respectively). The combined biomarker panel (cellular and protein markers) yields high sensitivity (90.5 %) and specificity (82.1 %) for predicting treatment efficacy. Disease control rate (DCR) and median progression free survival (PFS) are shown in the Table. Conclusions: To our knowledge, this pilot study is the first to detect three immune cell subtypes, regDC, Treg and CD4 + CD28 − cells, associated with clinical outcome in the treatment of PD-1/PD-L1 blockade. Profiling of immune cell subtypes and soluble immune checkpoint proteins can serve to identify therapeutic targets and biomarkers for treatment efficacy. We will report the data with further enrollment. [Table: see text]" @default.
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- W3032061859 date "2020-05-20" @default.
- W3032061859 modified "2023-10-14" @default.
- W3032061859 title "Novel biomarker panel based on cellular and soluble checkpoint proteins for PD-1/PD-L1 blockade treatment efficacy." @default.
- W3032061859 doi "https://doi.org/10.1200/jco.2020.38.15_suppl.3045" @default.
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