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.

Assessment of TILs, IDO-1, and PD-L1 in resected non-small cell lung cancer: an immunohistochemical study with clinicopathological and prognostic implications / Mandarano, Martina; Bellezza, Guido; Laura Belladonna, Maria; J Van den Eynde, Benoit; Chiari, Rita; Vannucci, Jacopo; Mondanelli, Giada; Ludovini, Vienna; Ferri, Ivana; Bianconi, Fortunato; Del Sordo, Rachele; Cagini, Lucio; Albini, Elisa; Metro, Giulio; Puma, Francesco; Sidoni, Angelo. - In: VIRCHOWS ARCHIV. - ISSN 0945-6317. - 474:2(2019), pp. 159-168. [10.1007/s00428-018-2483-1]

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

Jacopo Vannucci;
2019

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.
2019
IDO-1; Immunotherapy; Non-small cell lung cancer; PD-L1; Tumor-infiltrating lymphocytes
01 Pubblicazione su rivista::01a Articolo in rivista
Assessment of TILs, IDO-1, and PD-L1 in resected non-small cell lung cancer: an immunohistochemical study with clinicopathological and prognostic implications / Mandarano, Martina; Bellezza, Guido; Laura Belladonna, Maria; J Van den Eynde, Benoit; Chiari, Rita; Vannucci, Jacopo; Mondanelli, Giada; Ludovini, Vienna; Ferri, Ivana; Bianconi, Fortunato; Del Sordo, Rachele; Cagini, Lucio; Albini, Elisa; Metro, Giulio; Puma, Francesco; Sidoni, Angelo. - In: VIRCHOWS ARCHIV. - ISSN 0945-6317. - 474:2(2019), pp. 159-168. [10.1007/s00428-018-2483-1]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1479295
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