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Assessment of TILs, IDO-1, and PD-L1 in resected non-small cell lung cancer: an immunohistochemical study with clinicopathological and prognostic implications

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Abstract

Several cancers, especially non-small cell lung cancer (NSCLC), are able to escape the immunosurveillance of tumor-infiltrating lymphocytes (TILs); among the molecules involved, the indoleamine 2,3-dioxygenase 1 (IDO-1) and the programmed cell death ligand-1 (PD-L1) play a crucial role. These aspects are of great interest in the current immunotherapeutic era, therefore the current study analyses the TILs, IDO-1, and PD-L1 interactions and their correlations with clinicopathological parameters and prognosis in NSCLC. One hundred ninety-three NSCLC surgical specimens, formalin-fixed, and paraffin-embedded were assessed for TILs density, TILs localization, IDO-1 (clone 4.16H1), and PD-L1 (clone E1L3N) immunohistochemical expressions. This data was correlated with clinicopathological parameters, disease free, and overall survivals. IDO-1 and PD-L1 high expressions were related to the solid pattern of adenocarcinomas (respectively p = 0.036 and p = 0.026); high PD-L1 expression was correlated with squamous histotype (p = 0.048). IDO-1 overexpression correlated with former smokers (p = 0.041), higher adenocarcinoma stages (p = 0.039), and with both higher TILs density and PD-L1 expression (respectively p = 0.025 and p = 0.0003). A better prognosis was associated with TILs intratumoral or mixed localizations (p = 0.029). TILs localization affects NSCLC prognosis; the higher expression of IDO-1 and PD-L1 in poorly differentiated and more aggressive lung adenocarcinomas, as well as the correlation between high PD-L1 expression and squamous cell histotype, confirm the more efficient immunoescaping of these NSCLC subgroups.

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  1. Martina Mandarano and Guido Bellezza contributed equally to this work.

Authors and Affiliations

  1. Department of Experimental Medicine, Section of Anatomic Pathology and Histology, Medical School, University of Perugia, Perugia, Italy

    Martina Mandarano, Guido Bellezza, Ivana Ferri, Rachele Del Sordo & Angelo Sidoni

  2. Department of Experimental Medicine, University of Perugia, Perugia, Italy

    Maria Laura Belladonna, Giada Mondanelli & Elisa Albini

  3. Ludwig Institute for Cancer Research, de Duve Institute, Université catholique de Louvain, Louvain-la-Neuve, Belgium

    Benoit J Van den Eynde

  4. Department of Medical Oncology, Santa Maria della Misericordia Hospital, Perugia, Italy

    Rita Chiari, Vienna Ludovini & Giulio Metro

  5. Department of Thoracic Surgery, Medical School, University of Perugia, Perugia, Italy

    Jacopo Vannucci, Lucio Cagini & Francesco Puma

  6. Independent Researcher, Montefalco, Italy

    Fortunato Bianconi

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Mandarano, M., Bellezza, G., Belladonna, M.L. et al. Assessment of TILs, IDO-1, and PD-L1 in resected non-small cell lung cancer: an immunohistochemical study with clinicopathological and prognostic implications. Virchows Arch 474, 159–168 (2019). https://doi.org/10.1007/s00428-018-2483-1

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