miRNome profiling of lung cancer metastases revealed a key role for miRNA-PD-L1 axis in the modulation of chemotherapy response
Roberto Cuttano 1 , Tommaso Colangelo # 1 , Juliana Guarize # 2 , Elisa Dama 1 , Maria Pia Cocomazzi 1 , Francesco Mazzarelli 1 , Valentina Melocchi 1 , Orazio Palumbo 3 , Elena Marino 4 , Elena Belloni 5 , Francesca Montani 5 , Manuela Vecchi 6 7 8 , Massimo Barberis 9 , Paolo Graziano 10 , Andrea Pasquier 11 , Julian Sanz-Ortega 12 , Luis M Montuenga 11 13 , Cristiano Carbonelli 14 , Lorenzo Spaggiari 2 15 , Fabrizio Bianchi 16
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.
CITA DEL ARTÍCULO J Hematol Oncol. 2022 Dec 31;15(1):178. doi: 10.1186/s13045-022-01394-1