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oai:docta.ucm.es:20.500.14352/1163932025-01-28T01:01:18Zcom_20.500.14352_14col_20.500.14352_15

Aligning digital CD8+ scoring and targeted next-generation sequencing with programmed death ligand 1 expression: a pragmatic approach in early-stage squamous cell lung carcinoma Caminoa, Alejandra et al. Hernandez, Susana Conde Gallego, Esther Hernando Trancho, Florentino Sanz Ortega, Julián Paz-Ares Rodríguez, Luis Gonzaga Castro Fernández, Javier De López-Ríos Moreno, Fernando Aims: To study programmed death ligand 1 (PD-L1) expression, tumour-infiltrating T lymphocytes (TILs) and the molecular context in patients with early-stage squamous cell lung carcinomas (SCCs). Methods and results: The study included samples from 40 patients (discovery cohort) and 29 patients (validation cohort) diagnosed with early-stage SCC. PD-L1 immunohistochemistry (IHC) was performed with three commercially available clones (E1L3N, SP263 and SP142). CD8+ TILs were scored with a digital algorithm. All tumours were analysed with targeted next-generation sequencing (NGS). Additionally, TP53 mutations were investigated with direct sequencing. In both cohorts, we observed a significant association between CD8+ TILs density and high PD-L1 IHC expression in tumour cells (TCs). Furthermore, high SP142 PD-L1 expression in immune cells (ICs) was also associated significantly with CD8+ TILs density. Therefore, CD8+ TILs density discriminated between patients with high versus low PD-L1 IHC expression with excellent sensitivity and specificity. Interestingly, the highest percentages of PD-L1-positive TCs with the three antibodies were found in samples with cyclin-dependent kinase 6 (CDK6) amplification, with high amplification of proto-oncogene C-Myc (CMYC) or with cyclin D1-PI3 kinase subunit alpha (CCND1-PIK3CA) co-amplification. High SP142 PD-L1 IHC expression in ICs showed a non-significant correlation with TP53 mutations. Conversely, most cases with fibroblast growth factor receptor 1 (FGFR1) amplification were negative for all PD-L1 clones. Conclusions: Our preliminary results support the use of digital CD8+ TILs scoring and targeted NGS alongside PD-L1 expression. The approach presented herein could help define patients with SCCs candidates to immune checkpoints inhibitors. 2025-01-27T16:07:10Z 2025-01-27T16:07:10Z 2025-01-27T16:07:10Z 2018-01-01 journal article https://hdl.handle.net/20.500.14352/116393 XXXX-XXXX 10.1111/his.13346 eng Conde E, Caminoa A, Dominguez C, Calles A, Walter S, Angulo B, Sánchez E, Alonso M, Jimenez L, Madrigal L, Hernando F, Sanz-Ortega J, Jimenez B, Garrido P, Paz-Ares L, de Castro J, Hernandez S, Lopez-Rios F. Aligning digital CD8+ scoring and targeted next-generation sequencing with programmed death ligand 1 expression: a pragmatic approach in early-stage squamous cell lung carcinoma. Histopathology. 2018 Jan;72(2):270-284. doi: 10.1111/his.13346. Epub 2017 Nov 3. PMID: 28815764. http://creativecommons.org/licenses/by/4.0/ open access Attribution 4.0 International Wiley