Abstract

IntroductionThe immune status of the tumor microenvironment is extremely complex. One single immune feature cannot reflect the integral immune status, and its prognostic value was limited. We postulated that the immune signature based on multiple immuno-features could markedly improve the prediction of post-chemoradiotherapeutic survival in inoperable locally advanced non-small-cell lung cancer (LA-NSCLC) patients.MethodsIn this study, 100 patients who were diagnosed as having inoperable LA-NSCLC between January 2005 and January 2016 were analyzed. A five immune features-based signature was then constructed using the nested repeat 10-fold cross validation with least absolute shrinkage and selection operator (LASSO) Cox regression model. Nomograms were then established for predicting prognosis.ResultsThe immune signature combining five immuno-features was significantly associated with overall survival (OS) and progression-free survival (PFS) (P = 0.002 and P = 0.014, respectively) in patients with inoperable LA-NSCLC, and at a cutoff of −0.05 stratified patients into two groups with 5-year OS rates of 39.8 and 8.8%, and 2-year PFS rates of 22.2 and 5.5% for the high- and low-immune signature groups, respectively. Integrating immune signature, we proposed predictive nomograms that were better than the traditional TNM staging system in terms of discriminating ability (OS: 0.692 vs. 0.588; PFS: 0.672 vs. 0.586, respectively) or net weight classification (OS: 32.96%; PFS: 9.22%), suggesting that the immune signature plays a significant role in improving the prognostic value.ConclusionMultiple immune features-based immune signature could effectively predict recurrence and survival of inoperable LA-NSCLC patients and complemented the prognostic value of the TNM staging system.

Highlights

  • The immune status of the tumor microenvironment is extremely complex

  • The immune signature combining five immuno-features was significantly associated with overall survival (OS) and progression-free survival (PFS) (P = 0.002 and P = 0.014, respectively) in patients with inoperable LA-non-small-cell lung cancer (NSCLC), and at a cutoff of −0.05 stratified patients into two groups with 5-year OS rates of 39.8 and 8.8%, and 2-year PFS rates of 22.2 and 5.5% for the high- and low-immune signature groups, respectively

  • Integrating immune signature, we proposed predictive nomograms that were better than the traditional TNM staging system in terms of discriminating ability (OS: 0.692 vs. 0.588; PFS: 0.672 vs. 0.586, respectively) or net weight classification (OS: 32.96%; PFS: 9.22%), suggesting that the immune signature plays a significant role in improving the prognostic value

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Summary

Introduction

The immune status of the tumor microenvironment is extremely complex. One single immune feature cannot reflect the integral immune status, and its prognostic value was limited. Most LA-NSCLC patients are unable to undergo surgery, and platinum-based chemotherapy combined with concurrent thoracic radiotherapy is the first-line treatment for this group of patients [3] Their prognosis is quite different, with a 2-year overall survival (OS) rate of 24%– 55% and a 5-year OS rate of 13–36% [4]. In the phase 3 PACIFIC study of patients with unresectable, stage III NSCLC without progression after chemoradiotherapy (CRT), durvalumab [an anti-programmed death ligand 1 (PDL1) antibody] demonstrated significant improvements versus placebo in the primary endpoints of progression-free survival (PFS) and OS [6]. It suggests the important role of immune status in LA-NSCLC patients

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