Single-cell mass cytometric analysis of peripheral immunity and multiplex plasma marker profiling of non-small cell lung cancer patients receiving PD-1 targeting immune checkpoint inhibitors in comparison with platinum-based chemotherapy

Frontiers in Immunology

Immunology

Klára Szalontai¹  László Tiszlavicz²  György Lázár³  József Furák³  József Á. Balog⁴  László G. Puskás⁵  Gábor J. Szebeni⁶  Patrícia Neuperger⁷  Nikolett Gémes⁷ 

[1] Csongrád County Hospital of Chest Diseases, Deszk, Hungary;Department of Pathology, University of Szeged, Szeged, Hungary;Department of Surgery, University of Szeged, Szeged, Hungary;Laboratory of Functional Genomics, HUN-REN Biological Research Centre, Szeged, Hungary;Laboratory of Functional Genomics, HUN-REN Biological Research Centre, Szeged, Hungary;Avicor Ltd., Szeged, Hungary;Laboratory of Functional Genomics, HUN-REN Biological Research Centre, Szeged, Hungary;Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary;CS-Smartlab Devices Ltd., Kozármisleny, Hungary;Laboratory of Functional Genomics, HUN-REN Biological Research Centre, Szeged, Hungary;PhD School in Biology, University of Szeged, Szeged, Hungary;

关键词: non-small cell lung cancer;    platinum-based chemotherapy;    PD-1 blocking;    Nivolumab;    Pembrolizumab;   

DOI  :  10.3389/fimmu.2023.1243233

 received in 2023-06-20, accepted in 2023-09-27,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionThe effect of platinum-based chemotherapy (Chem.) and second- or multiple- line immune checkpoint PD-1 blocking therapy by Nivolumab or Pembrolizumab (ICI) was assayed in the peripheral blood of non-small cell lung cancer (NSCLC) patients. MethodsFlow cytometry was used to detect NSCLC-related antigen binding IgG antibodies. The Luminex MagPix multiplex bead-based cytokine/chemokine detecting system was used to quantitatively measure 17 soluble markers in the plasma samples. Single-cell mass cytometry was applied for the immunophenotyping of peripheral leukocytes. ResultsThe incubation of patient derived plasma with human NSCLC tumor cell lines, such as A549, H1975, and H1650, detected NSCLC-specific antibodies reaching a maximum of up to 32% reactive IgG-positive NSCLC cells. The following markers were detected in significantly higher concentration in the plasma of Chem. group versus healthy non-smoker and smoker controls: BTLA, CD27, CD28, CD40, CD80, CD86, GITRL, ICOS, LAG-3, PD-1, PD-L1, and TLR-2. The following markers were detected in significantly higher concentration in the plasma of ICI group versus healthy non-smoker and smoker controls: CD27, CD28, CD40, GITRL, LAG-3, PD-1, PD-L1, and TLR-2. We showed the induction of CD69 and IL-2R on CD4+ CD25+ T-cells upon chemotherapy; the exhaustion of one CD8+ T-cell population was detected by the loss of CD127 and a decrease in CD27. CD19+CD20+, CD79B+, or activated B-cell subtypes showed CD69 increase and downregulation of BTLA, CD27, and IL-2R in NSCLC patients following chemotherapy or ICI. DiscussionPeripheral immunophenotype caused by chemotherapy or PD-1 blocking was shown in the context of advanced NSCLC.

【 授权许可】

Unknown   
Copyright © 2023 Neuperger, Szalontai, Gémes, Balog, Tiszlavicz, Furák, Lázár, Puskás and Szebeni