1274PD - Analysis of immunoregulatory biomarkers in early stages of Non-Small Cell Lung Cancer

Date 11 September 2017
Event ESMO 2017 Congress
Session Non-metastatic NSCLC and other thoracic malignancies
Topics Cancer in Adolescents
Non-Small-Cell Lung Cancer, Early Stage
Cancer Immunology and Immunotherapy
Lung and other Thoracic Tumours
Presenter Andrea Moreno Manuel
Citation Annals of Oncology (2017) 28 (suppl_5): v453-v456. 10.1093/annonc/mdx381
Authors A. Moreno Manuel1, S. Calabuig Fariñas2, A. HERREROS POMARES1, S. Gallach Garcia3, F. Aranda4, A. Blasco5, E. Carreras4, F. Lozano6, A. Cunquero Tomas7, M. Martorell8, E. Jantus-Lewintre9, C. Camps Herrero10
  • 1Laboratorio De Oncología Molecular, Fundación para la Investigación, Hospital General Universitario de Valencia, 46014 - Valencia/ES
  • 2Laboratorio De Oncología Molecular, Fundación Para La Investigación, Hospital General Universitario De Valencia - Ciberonc;, Departamento de Patología, Universitat de València, 46014 - Valencia/ES
  • 3Laboratorio De Oncología Molecular, Fundación de Investigación Hospital General Universitario de Valencia-CIBERONC, 46014 - Valencia/ES
  • 4Immunoreceptors Of The Innate And Adaptative System, Institut d’Investigacions Biomèdiques August Pi i Sunyer, 08036 - Barcelona/ES
  • 5Servicio De Oncología Médica, Hospital General Universitario de Valencia-CIBERONC, 46014 - Valencia/ES
  • 6Servei D’immunologia, Centre De Diagnòstic Biomèdic, Hospital Clínic De Barcelona, Immunoreceptors of the Innate and Adaptive System, Institut d’Investigacions Biomèdiques August Pi i Sunyer; Departament de Biomedicina, Facultat de Medicina, Universitat de Barcelona., 08036 - Barcelona/ES
  • 7Servicio De Oncología Médica, Hospital General Universitario de Valencia, 46014 - Valencia/ES
  • 8Servicio De Anatomía Patológica, Hospital General Universitario De Valencia;, Departamento de Patología, Universidad de Valencia, 46014 - Valencia/ES
  • 9Laboratorio De Oncología Molecular, Fundación Para La Investigación, Hospital General Universitario De Valencia - Ciberonc;, Departamento de Biotecnología, Universidad Politécnica de Valencia, 46014 - Valencia/ES
  • 10Laboratorio De Oncología Molecular, Fundación Para La Investigación, Hospital General Universitario De Valencia - Ciberonc;, Servicio de Oncología Médica, Hospital General Universitario de Valencia; Departamento de Medicina, Universidad de Valencia;, 46014 - Valencia/ES

Abstract

Background

The study of the tumour microenvironment is leading to a better understanding of the evasion of immune surveillance and the development of new therapies. This research focuses on the analysis of immunoregulatory genes as potential prognostic biomarkers in resectable non-small cell lung cancer (NSCLC).

Methods

The expression of 8 genes involved in immune-regulation (PD-L1, PD-L2, IDO-1, IDO-2, ICOS-LG, CD5, CD6 and CD200) was analysed by RTqPCR in 257 paired fresh frozen tumour and normal tissue samples of resected NSCLC. Relative expression was calculated by Pfaffl formulae using ACTB, CDKN1B and GUSB as endogenous controls. Non-parametric tests were used for correlations between clinico-pathological and analytical variables and survival was assessed by Kaplan-Meier curves (long rank-test), considering significant p 

Results

Patient`s median age was 64 years, 82% were males, 88% were former or current smokers, 47% were adenocarcinomas (ADC). Patients with higher expression of CD5 and IDO2 had a significant increase in overall survival (OS, 53.3 vs NR months, p = 0.032; 51.9 vs NR months, p = 0.049, respectively). A signature combining the expression of CD5 and IDO2 was able to better prognosticate survival (40.4 vs NR months, p = 0.028). The multivariate analysis (including clinico-pathological and analytical variables) showed that this signature has independent prognostic information OS (HR = 0.553 [0.344-0.887], p = 0.016). Moreover, in the subgroup of ADC increased expression of CD5 and IDO2 was associated with longer OS as well as increased relapse-free survival (RFS, 19.1 vs NR months, p = 0.045; 18.8 and 67.0 months, p = 0.029, respectively). The multivariate analysis established this gene signature as an independent prognostic biomarker for OS (HR = 0.380 [0.166-0.872]; p = 0.026) and RFS (HR = 0.288 [0.139-0.597]; p = 0.002).

Conclusions

The analyses revealed the prognostic value of CD5 and IDO2, being their combination an independent prognostic marker in resectable NSCLC. Supported by grants from FEDER and PI12-02838 and PI15-00753 from ISCIII.

Clinical trial identification

Legal entity responsible for the study

Fundación para la Investigación del Hospital General Universitario de Valencia

Funding

Supported by grants from FEDER and PI12-02838 and PI15-00753 from ISCIII.

Disclosure

All authors have declared no conflicts of interest.