Paradoxical prognostic phenomenon of plasma T‑cell‑derived circulating DNA level in advanced non‑small cell lung cancer

• P. Sitthideatphaiboon ^[1] ; S. Santisukwongchote ^[2] ; S. Khunsri ^[1] ; C. Sathitruangsak ^[1] ; P. Chantranuwat ^[2] ; C. Vinayanuwattikun ^[1] ; V. Sriuranpong ^[1]
  1. [1] Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and The King Chulalongkorn Memorial Hospital, 1873 Rama IV road, Pathumwan, Bangkok 10330, Thailand
  2. [2] Department of Pathology, Faculty of Medicine, Chulalongkorn University and The King Chulalongkorn Memorial Hospital, 1873 Rama IV road, Pathumwan, Bangkok 10330, Thailand
• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 22, Nº. 7, 2020, págs. 1117-1125
• Idioma: inglés
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• Resumen

  • BackgroundNon-tumor-derived circulating DNA (nt-cirDNA) of advanced non-small cell lung cancer (NSCLC), with unclear origination, is associated with prognosis. We hypothesized that a part of nt-cirDNA release from CD3 or CD8 tumor-infiltrating lymphocytes (TILs) could have clinical implications.MethodTo investigate the feasibility of T-cell-derived circulating DNA (T-cirDNA) detection, real-time PCR with Taqman assay-specific rearranged TCRβ CDR3 region was conducted in plasma of 103 advanced NSCLC. CD3 and CD8-specific immunohistochemistry from biopsy specimen, was reviewed by one blinded pathologist to the T-cirDNA results. Prognostic impact including demographic characteristics was integrated into the model.ResultsCirculating DNA was detectable in 100 patients with median of 4 ng ml−1, while median of plasma T-cirDNA was 1.71 pg ml−1. Median %ratio of T-cirDNA/cirDNA was 0.02%. T-cirDNA was categorized by %ratio of T-cirDNA/cirDNA as undetectable, low (≤ 1%) and high (> 1%). Paradoxical prognostic impact of T-cirDNA/cirDNA was observed. Undetectable and high T-cirDNA/cirDNA translated to independent favorable prognostic outcome, HR of 0.54 [95% CI 0.30–0.96] and 0.41 [95% CI 0.21–0.80], respectively. 43 patients were assessed for CD3/CD8 TILs and PD-L1. High intratumoral CD3/CD8 TILs but not stromal CD3 TILs was correlated with high T-cirDNA/cirDNA representing active T-lymphocyte activity to eliminate cancer cells. While the prognosis of undetectable T-cirDNA/cirDNA, represents inactivated naïve T-cell, was determined by the presence of EGFR mutation and had long durable response of EGFR inhibitors.ConclusionT-cirDNA could be a novel biomarker representing adaptive immune resistance in NSCLC patients. Further exploration as a predictive biomarker for EGFR inhibitors in setting of EGFR mutation might be warranted.