Imbalance of Circulating Follicular Regulatory and Follicular Helper T Cell Subpopulations Is Associated with Disease Progression and Serum CYFRA 21-1 Levels in Patients with Non-small Cell Lung Cancer

Curr Med Sci. 2024 Feb;44(1):102-109. doi: 10.1007/s11596-023-2810-x. Epub 2023 Dec 11.

Abstract

Objective: This study aimed to investigate the changes of follicular helper T (TFH) and follicular regulatory T (TFR) cell subpopulations in patients with non-small cell lung cancer (NSCLC) and their significance.

Methods: Peripheral blood was collected from 58 NSCLC patients at different stages and 38 healthy controls. Flow cytometry was used to detect TFH cell subpopulation based on programmed death 1 (PD-1) and inducible co-stimulator (ICOS), and TFR cell subpopulation based on cluster determinant 45RA (CD45RA) and forkhead box protein P3 (FoxP3). The levels of interleukin-10 (IL-10), interleukin-17a (IL-17a), interleukin-21 (IL-21), and transforming growth factor-β (TGF-β) in the plasma were measured, and changes in circulating B cell subsets and plasma IgG levels were also analyzed. The correlation between serum cytokeratin fragment antigen 21-1 (CYFRA 21-1) levels and TFH, TFR, or B cell subpopulations was further explored.

Results: The TFR/TFH ratio increased significantly in NSCLC patients. The CD45RA+FoxP3int TFR subsets were increased, with their proportions increasing in stages II to III and decreasing in stage IV. PD-1+ICOS+TFH cells showed a downward trend with increasing stages. Plasma IL-21 and TGF-β concentrations were increased in NSCLC patients compared with healthy controls. Plasmablasts, plasma IgG levels, and CD45RA+FoxP3int TFR cells showed similar trends. TFH numbers and plasmablasts were positively correlated with CYFRA 21-1 in stages I-III and negatively correlated with CYFRA 21-1 in stage IV.

Conclusion: Circulating TFH and TFR cell subpopulations and plasmablasts dynamically change in different stages of NSCLC, which is associated with serum CYFRA 21-1 levels and reflects disease progression.

Keywords: follicular helper T cells; follicular regulatory T cells; non-small cell lung cancer; progression.

MeSH terms

  • Antigens, Neoplasm*
  • Carcinoma, Non-Small-Cell Lung*
  • Disease Progression
  • Forkhead Transcription Factors
  • Humans
  • Immunoglobulin G
  • Keratin-19*
  • Lung Neoplasms*
  • Programmed Cell Death 1 Receptor
  • T Follicular Helper Cells
  • Transforming Growth Factor beta

Substances

  • antigen CYFRA21.1
  • Programmed Cell Death 1 Receptor
  • Forkhead Transcription Factors
  • Transforming Growth Factor beta
  • Immunoglobulin G
  • Antigens, Neoplasm
  • Keratin-19