RT Journal Article
T1 Interferon gamma, an important marker of response to immune checkpoint blockade in non-small cell lung cancer and melanoma patients
A1 Karachaliou, Niki
A1 Gonzalez-Cao, Maria
A1 Crespo, Guillermo
A1 Drozdowskyj, Ana
A1 Aldeguer, Erika
A1 Gimenez-Capitan, Ana
A1 Teixido, Cristina
A1 Angel Molina-Vila, Miguel
A1 Viteri, Santiago
A1 De los Llanos Gil, Maria
A1 Martin Algarra, Salvador
A1 Perez-Ruiz, Elisabeth
A1 Marquez-Rodas, Ivan
A1 Rodriguez-Abreu, Delvys
A1 Blanco, Remedios
A1 Puertolas, Teresa
A1 Angeles Royo, Maria
A1 Rosell, Rafael
K1 Immunotherapy
K1 interferon-gamma
K1 PD-1
K1 PD-L1
K1 lung cancer
K1 melanoma
K1 Pd-1 blockade
K1 Open-label
K1 Ifn-gamma
K1 T-cells
K1 Clinical-response
K1 Ctla-4 blockade
K1 Viral mimicry
K1 Double-blind
K1 Expression
K1 Chemotherapy
AB Background: Programmed death-ligand 1 (PD-L1) may be induced by oncogenic signals or can be upregulated via interferon gamma (IFN-gamma). We have explored whether the expression of IFNG, the gene encoding IFN-gamma, 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-gamma 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.
PB Sage publications ltd
SN 1758-8340
YR 2018
FD 2018-01-18
LK https://hdl.handle.net/10668/26708
UL https://hdl.handle.net/10668/26708
LA en
DS RISalud
RD Apr 6, 2025