Virchows Archiv

, Volume 474, Issue 2, pp 159–168 | Cite as

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

  • Martina MandaranoEmail author
  • Guido Bellezza
  • Maria Laura Belladonna
  • Benoit J Van den Eynde
  • Rita Chiari
  • Jacopo Vannucci
  • Giada Mondanelli
  • Vienna Ludovini
  • Ivana Ferri
  • Fortunato Bianconi
  • Rachele Del Sordo
  • Lucio Cagini
  • Elisa Albini
  • Giulio Metro
  • Francesco Puma
  • Angelo Sidoni
Original Article


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.


Non-small cell lung cancer Tumor-infiltrating lymphocytes IDO-1 PD-L1 Immunotherapy 


Compliance with ethical standards

This manuscript is not under consideration elsewhere. There are no financial disclosures for all authors or funding sources for the manuscript. The work has been prepared according to ethical adherence regarding the informed consent of the involved human participants (Number of Local Ethic Committee Decision: N. 2216/13).

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Martina Mandarano
    • 1
    Email author
  • Guido Bellezza
    • 1
  • Maria Laura Belladonna
    • 2
  • Benoit J Van den Eynde
    • 3
  • Rita Chiari
    • 4
  • Jacopo Vannucci
    • 5
  • Giada Mondanelli
    • 2
  • Vienna Ludovini
    • 4
  • Ivana Ferri
    • 1
  • Fortunato Bianconi
    • 6
  • Rachele Del Sordo
    • 1
  • Lucio Cagini
    • 5
  • Elisa Albini
    • 2
  • Giulio Metro
    • 4
  • Francesco Puma
    • 5
  • Angelo Sidoni
    • 1
  1. 1.Department of Experimental Medicine, Section of Anatomic Pathology and Histology, Medical SchoolUniversity of PerugiaPerugiaItaly
  2. 2.Department of Experimental MedicineUniversity of PerugiaPerugiaItaly
  3. 3.Ludwig Institute for Cancer Research, de Duve InstituteUniversité catholique de LouvainLouvain-la-NeuveBelgium
  4. 4.Department of Medical OncologySanta Maria della Misericordia HospitalPerugiaItaly
  5. 5.Department of Thoracic Surgery, Medical SchoolUniversity of PerugiaPerugiaItaly
  6. 6.Independent ResearcherMontefalcoItaly

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