Interferon gamma, an important marker of response to immune checkpoint blockade in non-small cell lung cancer and melanoma patients
| Autor: | Delvys Rodriguez-Abreu, Ana Giménez-Capitán, Maria de los Llanos Gil, Santiago Viteri, Ana Drozdowskyj, G. Crespo, Maria Gonzalez-Cao, Cristina Teixidó, Ivan Marquez-Rodas, Miguel Angel Molina-Vila, Rafael Rosell, Erika Aldeguer, Remedios Blanco, Teresa Puertolas, Niki Karachaliou, Salvador Martin Algarra, Elisabeth Pérez-Ruiz, Maria Angeles Royo |
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| Rok vydání: | 2018 |
| Předmět: |
PD-L1
0301 basic medicine medicine.medical_treatment lcsh:RC254-282 Interferon-gamma 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation PD-1 melanoma Medicine Interferon gamma Lung cancer Melanoma Original Research biology business.industry Immunotherapy lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease Immune checkpoint Blockade lung cancer 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer research biology.protein interferon-gamma business medicine.drug |
| Zdroj: | Therapeutic Advances in Medical Oncology r-FISABIO. Repositorio Institucional de Producción Científica instname r-IGTP. Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol r-FISABIO: Repositorio Institucional de Producción Científica Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO) Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid Consejería de Sanidad de la Comunidad de Madrid Therapeutic Advances in Medical Oncology, Vol 10 (2018) |
| ISSN: | 1758-8359 1758-8340 |
| Popis: | Background: Programmed death-ligand 1 (PD-L1) may be induced by oncogenic signals or can be upregulated via interferon gamma (IFN-γ). We have explored whether the expression of IFNG, the gene encoding IFN-γ, is associated with clinical response to the immune checkpoint blockade in non-small cell lung cancer (NSCLC) and melanoma patients. The role of inflammation-associated transcription factors STAT3, IKBKE, STAT1 and other associated genes has also been examined. Methods: Total RNA from 17 NSCLC and 21 melanoma patients was analyzed by quantitative reverse transcription PCR. STAT3 and Rantes, YAP1 and CXCL5, DNMT1, RIG1 and TET1, EOMES, IFNG, PD-L1 and CTLA4, IKBKE and NFATC1 mRNA were examined. PD-L1 protein expression in tumor and immune cells and stromal infiltration of CD8+ T-cells were also evaluated. Progression-free survival and overall survival were estimated. Results: A total of 17 NSCLC patients received nivolumab and 21 melanoma patients received pembrolizumab. Progression-free survival with nivolumab was significantly longer in NSCLC patients with high versus low IFNG expression (5.1 months versus 2 months, p = 0.0124). Progression-free survival with pembrolizumab was significantly longer in melanoma patients with high versus low IFNG expression (5.0 months versus 1.9 months, p = 0.0099). Significantly longer overall survival was observed for melanoma patients with high versus low IFNG expression (not reached versus 10.2 months p = 0.0183). There was a trend for longer overall survival for NSCLC patients with high versus low IFNG expression. Conclusions: IFN-γ is an important marker for prediction of response to immune checkpoint blockade. Further research is warranted in order to validate whether IFNG is more accurate than PD-L1. |
| Databáze: | OpenAIRE |
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