Predictive/prognostic value of circulating regulatory T cell subset in untreated non-small lung cancer patients

Background

Regulatory T-cells (Treg) are highly heterogeneous populations with immune suppressive properties and their role in NSCLC is unknown. The frequency and functionality of the different Treg subtypes in the peripheral blood (PB) of NSCLC patients, as well as their correlation with the patients' clinical outcome was investigated.

Methods

PB from 156 chemotherapy-naive patients with stage III/IV NSCLC and 31 healthy donors (HD) was analyzed with flow cytometry for the presence of the different CD4⁺ Treg subsets [naïve: CD25^highCD127^−/lowCD152⁻FoxP3^lowCD45RO⁻, effector: CD25^highCD127^−/lowCD152⁺ FoxP3^low CD45RO⁺ and terminal effector: CD25^highCD127⁻CD152⁺FoxP3⁺CD45RO⁺]. Their functionality was tested based on TGF-� and IL-10 production. The patients' clinical outcome (PFS and OS) was correlated with the frequency of Treg subtypes (high vs low expression, according to their percentage > 90% percentile of the HD).

Results

All CD4⁺ Treg subsets exhibited a highly suppressive activity as revealed by their TGF-ß and IL-10 production. The percentages of naïve Tregs were increased in patients compared to HD (p = 0.02) and were associated with poor clinical outcome. Effector Tregs did not associated with response to treatment; Higher levels of Terminal effector Tregs were correlated with improved clinical response (p= 0.04). Normal levels of naïve and effector Treg, at baseline, were associated with longer PFS and OS compared to those with high levels (p= 0.03 and p = 0.02; p= 0.03 and p= 0.03, respectively). In contrast, high frequency of the terminal effector Treg, at baseline, was correlated with longer PFS (p = 0.03) and OS (p = 0.04) compared to low frequency.

Conclusions

It is demonstrated, for the first time, that particular CD4⁺ Treg subtypes are increased in NSCLC patients and are associated to the clinical outcome. Their depletion or blocking their migration to the tumour site may be an effective therapeutic strategy.

Clinical trial identification

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Legal entity responsible for the study

N/A

Funding

Laboratory of Translational Oncology, School of Medicine, University of Crete

Disclosure

All authors have declared no conflicts of interest.