The Role of Circulating T Follicular Helper Cells and Regulatory Cells in Non‐Small Cell Lung Cancer Patients

Abstract

T follicular helper (Tfh) cells and T follicular regulatory (Tfr) cells are identified as the new subset of immune cells. This study aims to investigate the role of circulating Tfh cells (cTfh) and Tfr (cTfr) cells in the pathogenesis of non-small cell lung cancer (NSCLC). A total of 27 NSCLC patients and 19 age and sex-matched healthy controls were enrolled. The percentage of cTfh and cTfr was detected by flow cytometric analysis. Compared to healthy controls, a significantly higher percentage of both cTfh and cTfr cells were observed in NSCLC patients (for cTfh, 18.88% ± 16.84% versus 5.98% ± 3.70%, P < 0.01; for cTfr, 2.67% ± 2.20% versus 1.14% ± 0.76%, P < 0.01). Furthermore, there was a positive correlation between cTfh/cTfr ratio and age in NSCLC patients (P < 0.05). When taking age 60 as a cut-off, the percentage of both cTfh cells and cTfr cells were higher in older patients than younger patients. Moreover, our data showed there was lower percentage of cTfh cells in NSCLC patients with early stage disease (I and II) (12.10% ± 12.22%) than that in advanced stage disease (III and IV) (30.41% ± 17.87%) (P < 0.01). However, no significant relationship was observed between cTfr cells and clinical stage in NSCLC patients. A higher percentage of cTfh cells was observed in patients with squamous cell carcinoma compared with adenocarcinoma (31.70% ± 20.73% versus. 13.48% ± 11.78%, P < 0.05). Taken together, there was significantly higher percentage of cTfh and cTfr cells in NSCLC patients. cTfh and cTfr cells might play an important role in the pathogenesis of NSCLC patients.

Control of Germinal Center Responses by T-Follicular Regulatory Cells

“…Increased numbers of activated ICOS + CXCR5 + Tfr are seen in the blood of non-small cell lung cancer patients although this did not correlated with disease stage (84). Tfr are also enriched in the lymph nodes of diffuse large B cell lymphoma (DLBCL) patients and the proportion of Tfr was reduced in patients with more advanced stage disease (85).…”

Follicular regulatory T cells: a novel target for immunotherapy?

“…The expansion of Tfr cells in ageing is corroborated in patients with NSCLC and IgG4‐RD . The percentages of cTfr cells and cTfh cells are higher in patients older than 60 years, but the cTfr/cTfh ratio is decreased with age . Nevertheless, the suppressive capacity of Tfr cells decreases with ageing .…”

“…Although the emphasis of Tfr‐cell studies is mainly on AIDs, vaccine responses and other diseases including infections, cancers, allergies, chronic graft rejection/graft‐versus‐host disease (GVHD) and acute respiratory distress syndrome (ARDS) have also been under investigation (shown in Table ).…”

“…In addition, Tfr cells from ovarian cancer patients exhibit higher TGF‐β (TGFB1) and IL‐10 (IL10) gene transcription levels, particularly the tumor‐infiltrating Tfr cells . The frequency of Tfr cells is not correlated with metastasis or the progression of breast cancer, whereas the frequency of cTfh cells is correlated with clinical stage and histological subtypes of NSCLC patients . Notably, when cocultured with CD8 + T cells in ovarian cancer patients, Tfr cells inhibit the activation of CD8 + T cells in an IL‐10–dependent manner, indicative of enhanced suppressive function …”

“…Increased frequencies of Tfr cells [89][90][91] and Tfh cells 90,91 are found in tumor-draining LNs 91 and peripheral blood 89,90 from patients with breast cancer, 91 non-small-cell lung cancer (NSCLC) 90 and ovarian carcinoma. 89 Tumor-infiltrating Tfr cells exhibit a higher proportion than cTfr cells.…”