Locally advanced non-small cell lung cancer (NSCLC) is frequent at diagnosis and requires multimodal treatment approaches. Neoadjuvant chemotherapy (NACT) followed by surgery is the treatment of choice for operable locally advanced NSCLC (Stage IIIA). However, the majority of patients are NACT-resistant and show persistent lymph nodal metastases (LNmets) and an adverse outcome. Therefore, the identification of mechanisms and biomarkers of NACT resistance is paramount for ameliorating the prognosis of patients with Stage IIIA NSCLC. Here, we investigated the miRNome and transcriptome of chemo-naïve LNmets collected from patients with Stage IIIA NSCLC (N = 64). We found that a microRNA signature accurately predicts NACT response. Mechanistically, we discovered a miR-455-5p/PD-L1 regulatory axis which drives chemotherapy resistance, hallmarks metastases with active IFN-γ response pathway (an inducer of PD-L1 expression), and impacts T cells viability and relative abundances in tumor microenvironment (TME). Our data provide new biomarkers to predict NACT response and add molecular insights relevant for improving the management of patients with locally advanced NSCLC.

Cuttano, R., Colangelo, T., Guarize, J., Dama, E., Cocomazzi, M., Mazzarelli, F., et al. (2022). miRNome profiling of lung cancer metastases revealed a key role for miRNA-PD-L1 axis in the modulation of chemotherapy response. JOURNAL OF HEMATOLOGY & ONCOLOGY, 15(1) [10.1186/s13045-022-01394-1].

miRNome profiling of lung cancer metastases revealed a key role for miRNA-PD-L1 axis in the modulation of chemotherapy response

Dama, Elisa;
2022

Abstract

Locally advanced non-small cell lung cancer (NSCLC) is frequent at diagnosis and requires multimodal treatment approaches. Neoadjuvant chemotherapy (NACT) followed by surgery is the treatment of choice for operable locally advanced NSCLC (Stage IIIA). However, the majority of patients are NACT-resistant and show persistent lymph nodal metastases (LNmets) and an adverse outcome. Therefore, the identification of mechanisms and biomarkers of NACT resistance is paramount for ameliorating the prognosis of patients with Stage IIIA NSCLC. Here, we investigated the miRNome and transcriptome of chemo-naïve LNmets collected from patients with Stage IIIA NSCLC (N = 64). We found that a microRNA signature accurately predicts NACT response. Mechanistically, we discovered a miR-455-5p/PD-L1 regulatory axis which drives chemotherapy resistance, hallmarks metastases with active IFN-γ response pathway (an inducer of PD-L1 expression), and impacts T cells viability and relative abundances in tumor microenvironment (TME). Our data provide new biomarkers to predict NACT response and add molecular insights relevant for improving the management of patients with locally advanced NSCLC.
Articolo in rivista - Articolo scientifico
Chemotherapy; Gene expression; Lung cancer; microRNA; miR-455-5p; NSCLC; PD-L1;
English
31-dic-2022
2022
15
1
178
none
Cuttano, R., Colangelo, T., Guarize, J., Dama, E., Cocomazzi, M., Mazzarelli, F., et al. (2022). miRNome profiling of lung cancer metastases revealed a key role for miRNA-PD-L1 axis in the modulation of chemotherapy response. JOURNAL OF HEMATOLOGY & ONCOLOGY, 15(1) [10.1186/s13045-022-01394-1].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/400591
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