Gene expression profiles (GEPs) of immuno-oncologic pathways as predictors of response to checkpoint inhibitors in advanced NSCLC.

Autor:	De Marchi P; Oncoclinicas, Rio De Janeiro, Brazil; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil. Electronic address: pedrodemarchi@yahoo.com.br., Leal LF; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil; Barretos School of Health Sciences, Dr. Paulo Prata - FACISB, Barretos, SP, Brazil., da Silva LS; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil., Cavagna RO; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil., da Silva FAF; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil., da Silva VD; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil., da Silva EC; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil., Saito AO; ACCamargo Cancer Center, São Paulo, Brazil., de Lima VCC; ACCamargo Cancer Center, São Paulo, Brazil., Reis RM; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil; Life and Health Sciences Research Institute (ICVS), Medical School, University of Minho, Braga, Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal. Electronic address: ruireis.hcb@gmail.com.
Jazyk:	angličtina
Zdroj:	Translational oncology [Transl Oncol] 2024 Jan; Vol. 39, pp. 101818. Date of Electronic Publication: 2023 Oct 31.
DOI:	10.1016/j.tranon.2023.101818
Abstrakt:	Background: Immune checkpoint inhibitors (ICIs) revolutionized non-small-cell lung cancer (NSCLC) treatment. However, improving patients' selection for this therapy is needed. Gene expression profile (GEP) is a promising biomarker tool. We assessed the predictive value of 48 onco-immune GEPs in an NSCLC real-world scenario. Methods: Retrospective cohort of Brazilian NSCLC patients treated with ICIs in any line. GEP was assessed in FFPE tumor tissue using the nCounter PanCancer IO360 panel, comprising 770 cancer immune genes. Results: The median age of the 135 patients was 61 years old, most male (57.8 %), history of smoking (83.6 %), ECOG-PS 0-1 (88.7 %), clinical stage IV (91.9 %) and adenocarcinoma (65.1 %). First-line ICI in 40 % of cases, alone or in combination with chemotherapy. The median follow-up was 28 months, overall survival after starting immunotherapy (post-immunotherapy survival - PIS) was 17.8 months, and real-world progression-free survival was 5.5 months. The GEP analysis was possible in 66 patients. We found that 14 different GEPs associated with PIS, namely IDO1, PD-L2, Cytotoxicity, Cytotoxic Cells, IFN Downstream, CTLA4, PD-L1, TIGIT, Lymphoid, Immunoproteasome, Exhausted CD8, IFN Gamma, TIS and APM. TIS and IFN-γ were the most significant GEPs associated with favorable outcomes. The median PIS for patients with high TIS expression was 29.2 versus 15.5 months (HR 0.42; 95 %CI; 0.17-0.67; p<0.05) for those with low expression. Similar results were observed for IFN-γ. Conclusions: The TIS (tumor inflammation signature) and IFN-γ signatures constitute predictive biomarkers to identify patients with NSCLC patients who would possibly benefit from ICI therapies. Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023. Published by Elsevier Inc.)
Databáze:	MEDLINE
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