Increased CD8+CD28+ T cells independently predict better early response to stereotactic ablative radiotherapy in patients with lung metastases from non-small cell lung cancer

J Transl Med. 2019 Apr 11;17(1):120. doi: 10.1186/s12967-019-1872-9.

Abstract

Background: Stereotactic ablative radiotherapy (SABR) shows a remarkable local control of non-small cell lung cancer (NSCLC) metastases, partially as a result of host immune status. However, the predictors of immune cells for tumor response after SABR are unknown. To that effect, we investigated the ability of pre-SABR immune cells in peripheral blood to predict early tumor response to SABR in patients with lung metastases from NSCLC.

Methods: This study included 70 patients with lung metastases from NSCLC who were undergoing SABR. We evaluated the early tumor response 1 month and 6 months after SABR in these patients following RECIST 1.1 guidelines. Pre-SABR peripheral CD8+ T cell count, CD8+CD28+ T-cell count, CD8+CD28- T-cell count, CD4+ T-cell count, and Treg-cell count were measured using flow cytometry.

Results: Increased CD8+CD28+ T-cell counts (14.43 ± 0.65 vs. 10.21 ± 0.66; P = 0.001) and CD4/Treg ratio (16.96 ± 1.76 vs. 11.91 ± 0.74; P = 0.011) were noted in 1-month responsive patients, compared with non-responsive patients. In univariate logistic analyses, high CD8+CD28+ T-cell counts (OR 0.12, 95% CI 0.03-0.48; P = 0.003), CD4/Treg ratio (OR 0.24, 95% CI 0.06-0.90; P = 0.035), and BED10 (OR 0.91, 95% CI 0.84-0.99; P = 0.032) predicted a 1-month tumor response to SABR. According to multivariate logistic analyses, the CD8+CD28+ T-cell count predicted a 1-month tumor response to SABR (OR 0.19, 95% CI 0.04-0.90; P = 0.037) independently. Furthermore, we confirmed the independent predictive value of the CD8+CD28+ T-cell count in predicting tumor response to SABR in 41 patients 6 months after treatment (OR 0.08, 95% CI 0.01-0.85; P = 0.039).

Conclusions: A pre-SABR CD8+CD28+ T-cell count could predict early tumor response to SABR in patients with lung metastases from NSCLC. Larger, independently prospective analyses are warranted to verify our findings.

Keywords: Biomarker; Immunology; Lung metastases; Stereotactic ablative radiotherapy; Tumor response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • CD28 Antigens / metabolism*
  • CD8-Positive T-Lymphocytes / immunology*
  • Carcinoma, Non-Small-Cell Lung / immunology*
  • Carcinoma, Non-Small-Cell Lung / radiotherapy*
  • Female
  • Humans
  • Lung Neoplasms / secondary*
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Multivariate Analysis
  • ROC Curve
  • Radiosurgery*
  • T-Lymphocytes, Regulatory / immunology

Substances

  • CD28 Antigens