a0891cb51cf5ea6771a4b67ce8b415e9 ijms-25-12269.pdf 5e5aea00b76c25e91751b3628c16d491296e9359 ijms-25-12269.pdf 1611af121074417ccb3687cc32711431b1591e5d36da39e0c65fe6d92cbd34b2 ijms-25-12269.pdf Title: Prognostic Significance of PD-L1 Expression on Circulating Myeloid-Derived Suppressor Cells in NSCLC Patients Treated with Anti-PD-1/PD-L1 Checkpoint Inhibitors Subject: Even though anti-PD-1/PD-L1 immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) have improved survival, a high percentage of patients still do not respond to ICIs. Myeloid-derived suppressor cells (MDSCs) are circulating cells that express PD-L1 and can infiltrate and proliferate in the tumor microenvironment, inducing immunosuppression. By evaluating changes in PD-L1 expression of live peripheral blood MDSCs, we are able to define a new PD-L1 index, useful in predicting ICI escape in NSCLC patients before initiating anti-PD-1/PD-L1 immunotherapy. In this study, a cohort of 37 NSCLC patients was prospectively analyzed, obtaining independent PD-L1 indexes. In patients with a PD-L1 index > 5.88, progressive disease occurred in 58.33% of patients [median progression-free survival (PFS) = 5.73 months; 95%CI = 2.67–20.53], showing significant differences when compared with patients with a PD-L1 index 5.88, in whom 7.69% progressed and median PFS was not reached (NR); p-value = 0.0042. Overall survival (OS) was significantly worse in patients with a high vs. low PD-L1 index (41.67% vs. 76.92%; median OS = 18.03 months, 95%CI = 6.77–25.23 vs. NR, 95%CI = 1.87-NR; p-value = 0.035). The PD-L1 index can be applied to stratify NSCLC patients according to their probability of response to ICIs at baseline. In addition to quantifying tumoral expression, this index could be used to compare nonresponse to treatment. Keywords: PD-L1; immunotherapy; NSCLC; flow cytometry Author: Roser Salvia, Laura G. Rico, Teresa Morán, Jolene A. Bradford, Michael D. Ward, Ana Drozdowskyj, Joan Climent-Martí, Eva M. Martínez-Cáceres, Rafael Rosell and Jordi Petriz Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Fri Nov 15 09:51:31 2024 CET ModDate: Fri Nov 15 10:02:02 2024 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 13 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1450756 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- SSNIUI+VnURWPalladioL-Bold Type 1 Custom yes yes yes 10 0 YGHIWF+URWPalladioL-Bold Type 1 Custom yes yes yes 16 0 QKXQTO+URWPalladioL-Roma Type 1 Custom yes yes yes 22 0 RVISGP+URWPalladioL-Ital Type 1 Custom yes yes yes 27 0 KXDJCR+CMSY10 Type 1 Builtin yes yes yes 32 0 KORLVE+VnURWPalladioL Type 1 Custom yes yes yes 37 0 EHAKCM+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 83 0 EHAKDM+PalatinoLinotype CID TrueType Identity-H yes yes yes 86 0 EHAKDN+PalatinoLinotype TrueType WinAnsi yes yes no 92 0 EHAKDP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 95 0 EHALHK+PalatinoLinotype TrueType MacRoman yes yes no 98 0 EHAKCM+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 111 0 EHAKDM+PalatinoLinotype CID TrueType Identity-H yes yes yes 114 0 EHAKDN+PalatinoLinotype TrueType WinAnsi yes yes no 120 0 EHAKDP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 123 0 EHALHK+PalatinoLinotype TrueType MacRoman yes yes no 126 0 EHBEJE+Arial,Bold CID TrueType Identity-H yes yes yes 141 0 EHBEKG+Arial,BoldItalic TrueType WinAnsi yes yes no 147 0 EHBELG+Arial CID TrueType Identity-H yes yes yes 150 0 EHAKCM+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 156 0 EHAKDM+PalatinoLinotype CID TrueType Identity-H yes yes yes 159 0 EHAKDN+PalatinoLinotype TrueType WinAnsi yes yes no 165 0 EHAKDP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 168 0 EHALHK+PalatinoLinotype TrueType MacRoman yes yes no 171 0 EHBEBG+Calibri CID TrueType Identity-H yes yes yes 174 0 EHBEJE+Arial,Bold CID TrueType Identity-H yes yes yes 191 0 EHBEKG+Arial,BoldItalic TrueType WinAnsi yes yes no 197 0 EHBELG+Arial CID TrueType Identity-H yes yes yes 200 0 EHAKCM+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 206 0 EHAKDM+PalatinoLinotype CID TrueType Identity-H yes yes yes 209 0 EHAKDN+PalatinoLinotype TrueType WinAnsi yes yes no 215 0 EHAKDP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 218 0 EHALHK+PalatinoLinotype TrueType MacRoman yes yes no 221 0 EHBEBG+Calibri CID TrueType Identity-H yes yes yes 224 0 OQIVQT+EURM10 Type 1 Builtin yes yes yes 235 0 JHYTSG+CMR10 Type 1 Builtin yes yes yes 246 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-01-11 02:45:28 CET RepresentationInformation: ijms-25-12269.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-01-10 11:05:43 CET Size: 1450756 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 409 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Results Destination: section.2 Children: Item: Title: Patients Characteristics Destination: subsection.2.1 Item: Title: Clinical Outcome Destination: subsection.2.2 Item: Title: PD-L1 Index of Myeloid-Derived Suppressor Cells Is a Predictor of Clinical Outcome Destination: subsection.2.3 Item: Title: Discussion Destination: section.3 Item: Title: Materials and Methods Destination: section.4 Children: Item: Title: Patients Destination: subsection.4.1 Item: Title: Sample Preparation and Flow Cytometry Data Analysis Destination: subsection.4.2 Item: Title: Statistical Analysis Destination: subsection.4.3 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: appendix.A. Info: Title: Prognostic Significance of PD-L1 Expression on Circulating Myeloid-Derived Suppressor Cells in NSCLC Patients Treated with Anti-PD-1/PD-L1 Checkpoint Inhibitors Author: Roser Salvia, Laura G. Rico, Teresa Morán, Jolene A. Bradford, Michael D. Ward, Ana Drozdowskyj, Joan Climent-Martí, Eva M. Martínez-Cáceres, Rafael Rosell and Jordi Petriz Subject: Even though anti-PD-1/PD-L1 immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) have improved survival, a high percentage of patients still do not respond to ICIs. Myeloid-derived suppressor cells (MDSCs) are circulating cells that express PD-L1 and can infiltrate and proliferate in the tumor microenvironment, inducing immunosuppression. By evaluating changes in PD-L1 expression of live peripheral blood MDSCs, we are able to define a new PD-L1 index, useful in predicting ICI escape in NSCLC patients before initiating anti-PD-1/PD-L1 immunotherapy. In this study, a cohort of 37 NSCLC patients was prospectively analyzed, obtaining independent PD-L1 indexes. In patients with a PD-L1 index > 5.88, progressive disease occurred in 58.33% of patients [median progression-free survival (PFS) = 5.73 months; 95%CI = 2.67 20.53], showing significant differences when compared with patients with a PD-L1 index 5.88, in whom 7.69% progressed and median PFS was not reached (NR); p-value = 0.0042. Overall survival (OS) was significantly worse in patients with a high vs. low PD-L1 index (41.67% vs. 76.92%; median OS = 18.03 months, 95%CI = 6.77 25.23 vs. NR, 95%CI = 1.87-NR; p-value = 0.035). The PD-L1 index can be applied to stratify NSCLC patients according to their probability of response to ICIs at baseline. In addition to quantifying tumoral expression, this index could be used to compare nonresponse to treatment. 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