Cancers (Nov 2020)

Circulating Interleukin-4 Is Associated with a Systemic T Cell Response against Tumor-Associated Antigens in Treatment-Naïve Patients with Resectable Non-Small-Cell Lung Cancer

  • Seyer Safi,
  • Yoshikane Yamauchi,
  • Hans Hoffmann,
  • Wilko Weichert,
  • Philipp J. Jost,
  • Hauke Winter,
  • Thomas Muley,
  • Philipp Beckhove

DOI
https://doi.org/10.3390/cancers12123496
Journal volume & issue
Vol. 12, no. 12
p. 3496

Abstract

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Spontaneous T cell responses to tumor-associated antigens (TAs) in the peripheral blood of patients with non-small-cell lung cancer (NSCLC) may be relevant for postoperative survival. However, the conditions underlying these T cell responses remain unclear. We quantified the levels of 27 cytokines in the peripheral blood and tumor tissues from treatment-naïve patients with NSCLC (n = 36) and analyzed associations between local and systemic cytokine profiles and both TA-specific T cell responses and clinical parameters. We defined T cell responders as patients with circulating T cells that were reactive to TAs and T cell nonresponders as patients without detectable TA-specific T cells. TA-specific T cell responses were correlated with serum cytokine levels, particularly the levels of interleukin(IL)-4 and granulocyte colony-stimulating factor (G-CSF), but poorly correlated with the cytokine levels in tumor tissues. Nonresponders showed significantly higher serum IL-4 levels than responders (p = 0.03); the predicted probability of being a responder was higher for individuals with low serum IL-4 levels. In multivariable Cox regression analyses, in addition to IL-4 (hazard ratio (HR) 2.8 (95% confidence interval (CI): 0.78–9.9); p = 0.116), the age-adjusted IL-8 level (HR 3.9 (95% CI: 1.05–14.5); p = 0.042) predicted tumor recurrence. However, this study included data for many cytokines without adjustment for multiple testing; thus, the observed differences in IL-4 or IL-8 levels might be incidental findings. Therefore, additional studies are necessary to confirm these results.

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