Therapeutic Advances in Medical Oncology (Jan 2018)

Interferon gamma, an important marker of response to immune checkpoint blockade in non-small cell lung cancer and melanoma patients

  • Niki Karachaliou,
  • Maria Gonzalez-Cao,
  • Guillermo Crespo,
  • Ana Drozdowskyj,
  • Erika Aldeguer,
  • Ana Gimenez-Capitan,
  • Cristina Teixido,
  • Miguel Angel Molina-Vila,
  • Santiago Viteri,
  • Maria De Los Llanos Gil,
  • Salvador Martin Algarra,
  • Elisabeth Perez-Ruiz,
  • Ivan Marquez-Rodas,
  • Delvys Rodriguez-Abreu,
  • Remedios Blanco,
  • Teresa Puertolas,
  • Maria Angeles Royo,
  • Rafael Rosell

DOI
https://doi.org/10.1177/1758834017749748
Journal volume & issue
Vol. 10

Abstract

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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.