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. 2017 Jul;14(1):1133-1140.
doi: 10.3892/ol.2017.6191. Epub 2017 May 17.

Characterization of γδ T cells in patients with non-small cell lung cancer

Yi Bao  1   2 , Li Guo  1 , Juanfen Mo  1
Affiliations

Characterization of γδ T cells in patients with non-small cell lung cancer

Yi Bao et al. Oncol Lett. 2017 Jul.

Abstract

Systemic immune defects that are associated with disease progression exist in a variety of malignancies. γδ T cells are innate-like lymphocytes that do not require self-major histocompatibility complex-restricted priming. Ex vivo-expanded circulating γδ T cells exhibit promising antitumor activity and are a potential candidate for the treatment of various malignancies, including non-small cell lung cancer (NSCLC). In the present study, flow cytometry was used as a method to study the phenotypes and characteristics of γδ T cells. A lower frequency of circulating γδ T cells was observed in NSCLC patients than in healthy controls. In advanced NSCLC patients, γδ T cells were also detected in the pleural effusion, but the frequency of γδ T cells here was significantly lower than in the peripheral blood. Vδ1+and Vδ1-Vδ2- T cells represented the most enriched subsets in the pleural effusion. Moreover, the present study demonstrated that Vδ1+ T cells are a type of γδ T cells characterized by a cluster of differentiation (CD)3dim T-cell receptor (TCR)γδbright phenotype, whereas Vδ2+ T cells represent a CD3brightTCRγδdim phenotype, according to the fluorescence intensity of CD3 and γδTCR using flow cytometry. Finally, the present study reported a decrease in the expression of CD27 and CD28 molecules on the surface of circulating γδ T cells in NSCLC. The present data suggest the existence of a dysregulated repertoire of γδ T cells in NSCLC, which exhibit impaired activation and a reformed cytokine-releasing profile. Although the ex vivo expansion of γδ T cells may be a prospective therapeutic strategy in NSCLC patients, it remains necessary to clarify which subsets (Vδ1 or Vδ2) should be expanded and the sources from which γδ T cells should be generated.

Keywords: non-small cell lung cancer; peripheral blood; pleural effusion; γδ T cells.

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Figures

Figure 1.
Figure 1.
Retrospective analysis of the complete blood cell count in NSCLC patients. (A) A decrease was observed in the absolute number of lymphocytes in NSCLC patients (1.285×109±0.049×109/l) compared with healthy controls (2.065×109±0.051×109/l) (P<0.001). (B) An increase in the absolute number of monocytes was observed in NSCLC patients (0.484×109±0.022×109/l) compared with healthy controls (0.363±0.011) (P<0.001). ***P<0.001. NSCLC, non-small cell lung cancer; FSC, forward scatter; SSC, side scatter; TCR, T-cell receptor.
Figure 2.
Figure 2.
Identification and characterization of a population of γδ T cells and Vδ1+Vδ2+ subtypes in the lymphocytes. (A) Cells were gated as lymphocytes and then CD3+T cells. Subsequently, the presence of TCRγδ+ T cells was assessed in CD3+ T cells. In the population of CD3+TCRγδ+T cells, Vδ1+Vδ2+ and Vδ1−Vδ2−were further gated and analyzed. (B) The percentage of CD3+γδ T cells in NSCLC patients and healthy controls (4.16±0.44 vs. 6.40±0.77%, respectively; P<0.05). *P<0.05. NSCLC, non-small cell lung cancer; FSC, forward scatter; SSC, side scatter; TCR, T-cell receptor; CD, cluster of differentiation.
Figure 3.
Figure 3.
Comparison of γδ T cells and Vδ1Vδ2 subsets between the PB and pleural effusion in paired samples derived from advanced non-small cell lung cancer patients. (A) There was a decreased percentage of CD3+γδ+T cells in the pleural effusion compared with the PB (2.47±0.69 vs. 5.32±1.08%, respectively; P<0.05). (B) A higher percentage of Vδ2 cells were present in the population of CD3+γδ+T cells in the PB compared with the pleural effusion (36.01±8.25 vs. 8.16±2.38%, respectively; P<0.01). (C) There was a lower percentage of Vδ1 T cells in the PB than in the pleural effusion (44.54±8.49 vs. 64.78±5.50%, respectively; P<0.05). *P<0.05. **P<0.01. PB, peripheral blood; CD, cluster of differentiation.
Figure 4.
Figure 4.
Expression of CD3 and TCRγδ molecules on the surface of Vδ1 and Vδ2 T cell subsets in the circulation of NSCLC patients and healthy individuals. (A) The MFI of CD3 was decreased in Vδ1 cells compared with that in Vδ2 cells in the group of NSCLC patients (2,612±319.4 vs. 4,776±691.2 AU, respectively; P<0.01). (B) The MFI of CD3 in Vδ1+ cells was decreased compared with that in Vδ2 cells in the group of normal individuals (3,454±592.6 vs. 9,689±1,270 AU, respectively; P<0.001). (C) The MFI of TCRγδ in Vδ1 cells was increased compared with Vδ2 in the group of NSCLC patients (2,614±313.10 vs. 858±62.49 AU, respectively; P<0.001). (D) The MFI of TCRγδ in Vδ1 T cells was increased compared with that in Vδ2 cells in the group of normal individuals (3,724±725.20 vs. 1,351±182.8, respectively; P<0.01).**P<0.01. ***P<0.001. NSCLC, non-small cell lung cancer; MFI, mean fluorescence intensity; TCR, T-cell receptor; CD, cluster of differentiation.
Figure 5.
Figure 5.
Identification of the co-stimulatory markersCD27 and CD28 on the surface of CD3+γδ+T cells in patients with advanced NSCLC. (A) Cells were gated as lymphocytes and then CD3+γδ+T cells. Subsequently, the presence of TCRγδ+cells was assessed for in CD3+ T cells. In the population of CD3+γδ+T cells, the expression of CD27 and CD28 was further gated and analyzed. (B) There was a significantly increased frequency of CD27−CD28−CD3+γδ+T cells in the peripheral blood of NSCLC patients compared with healthy controls (40.2±5.7 vs. 11.9±4.8%, respectively; P<0.01). **P<0.01. NSCLC, non-small cell lung cancer; TCR, T-cell receptor; CD, cluster of differentiation.
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