39O - Immune checkpoints score and CD8+ T cells infiltration are independent prognostic biomarkers in resected NSCLC

Date 16 April 2015
Event ELCC 2015
Session Medical and surgical oncology
Topics Non-Small-Cell Lung Cancer, Metastatic
Translational Research
Presenter Marta Usó
Citation Annals of Oncology (2015) 26 (suppl_1): 10-14. 10.1093/annonc/mdv045
Authors M. Usó1, E. Jantus-Lewintre2, R. Sirera3, S. Calabuig-Fariñas2, A. Blasco4, R. Guijarro5, J. Forteza6, C. Camps1
  • 1Department Of Medicine, Universitat de València, 46010 - Valencia/ES
  • 2Molecular Oncology, Fundación Investigación Hospital General Universitario de Valencia, Valencia/ES
  • 3Department Of Biotechnology, Universitat Politècnica de València, Valencia/ES
  • 4Medical Oncology, Hospital General Universitario Valencia, Valencia/ES
  • 5Thoracic Surgery, Hospital General Universitario Valencia, Valencia/ES
  • 6Instituto Valenciano De Patología, Universidad Católica de Valencia, Valencia/ES

Abstract

Aim/Background

Due to the promising clinical results of immune checkpoints blockade, we have investigated the prognostic role of immune checkpoint expression markers and CD8+ T cells infiltration in resected NSCLC.

Methods

RNA was isolated from fresh-frozen lung specimens (tumor and normal) (n = 178). RTqPCR was performed to analyze the expression of CTLA4, PD1 and PDL1, and gene expression was normalized against CDKN1B, GUS and ACTB as endogenous control. These data were used to develop a gene expression score. The presence of CD8+cells was assessed in tumor and stroma compartments in 63 FFPE samples by immunohistochemistry. All statistical analyses were considered significant at p< 0.05.

Results

A multivariate model including CTLA4 and PD1 was created and absolute regression coefficients were used to calculate the immune checkpoints score (ICS): (PD1 x 0.116) + (CTLA4 x 0.0589). We found a significant association between high ICS and CD8+ infiltrating cells in the tumor compartment (p = 0.012). Kaplan-Meier survival analysis showed that patients with high ICS had longer overall survival (OS) [NR vs 40.4 months, p = 0.008] and longer progression free survival (PFS) [82.6 vs 23 months, p = 0.009]. Moreover, the presence of CD8+cells in the tumor compartment was significantly associated with better OS [73.9 vs 40.4 months, p = 0.021] and PFS [56.8 vs 23 months, p = 0.026]. Multivariate analysis indicated that ICS and CD8+ cells infiltration were independent biomarkers of prognosis (Table 1).

Results from multivariate Cox regression models

OS PFS
Variable HR 95% CI p HR 95% CI P
N = 178
KRAS status Mutated vs WT 2.984 1.338-6.659 0.008 3.807 1.764-8.214 0.001
Immune checkpoints score High vs low 0.308 0.156-0.609 0.001 0.527 0.298-0.933 0.028
N = 63
Tumoral CD8+ cells High vs Low 0.386 0.175-0.850 0.018 0.305 0.137-0.680 0.004

CI, confidence interval; HR, hazard ratio, p; p-value

Conclusions

The immune checkpoints score, based on the expression levels of CTLA4 and PD1, and the presence of CD8+ cells in the tumor compartment provide relevant prognostic information for a better characterization of early-stage NSCLC patients with strikingly different outcomes who may be candidates for immune-based therapies. Supported by grants PI12-02838 and RD12/0036/0025 from ISCIII.

Disclosure

All authors have declared no conflicts of interest.