Prognostic value of circulating regulatory T cell subsets in untreated non-small cell lung cancer patients

Κotsakis, Athanasios; Koinis, Filippos; Katsarou, Afroditi; Gioulbasani, Marianthi; Aggouraki, Despoina; Kentepozidis, Nikolaos; Vetsika, Eleni-Kyriaki

doi:10.1038/srep39247

Cited by 87 publications

(75 citation statements)

References 53 publications

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“…The higher percentages of Treg in cancer patients were caused by smoking behavior. However, lower Treg percentages predicted better survival in our patient cohort, which is in line with other reports [45]. This Treg-linked adverse prognosis could be a result of lymphocytic suppression.…”

Section: Discussionsupporting

confidence: 93%

Blood immune cell biomarkers in lung cancer

Riemann

Cwikowski

Turzer

et al. 2018

Clinical and Experimental Immunology

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Summary Characterization of host immune cell parameters prior to treatment is expected to identify biomarkers predictive of clinical outcome as well as to elucidate why some patients fail to respond to immunotherapy. We monitored blood immune cells from 58 patients with non‐small‐ cell lung cancer (NSCLC) undergoing surgery of the primary tumor and from 50 age‐matched healthy volunteers. Complete leukocyte blood count, the number of circulating dendritic cells (DC), HLA‐DRlow monocytes and several lymphocytic subpopulations were determined by eight‐color flow cytometry. Furthermore, the prognostic value of the immune cell parameters investigated was evaluated by patients’ survival analysis. Compared to the control group, blood of NSCLC patients contained more neutrophils resulting in a higher neutrophil‐to‐lymphocyte ratio (NLR), but a lower number of blood DC, in particular of plasmacytoid DC (pDC), natural killer (NK) cells and naive CD4+ and CD8+ T cells. Furthermore, a higher frequency of CD4+ regulatory T cells (Treg) and HLA‐DRlow monocytes was detected, and smoking had a significant impact on these values. HLA‐DRlow monocytes were positively correlated to the number of neutrophils, monocytes and NLR, but negatively associated with the number of pDC and naive CD4+ T cells. The frequency of Treg, HLA‐DRlow monocytes and naive CD4+ and CD8+ T cells as well as the ratios of CD4/HLA‐DRlow monocytes and HLA‐DRlow monocytes/pDC correlated with patient’s overall survival. Next to Treg, HLA‐DRlow monocytes and naive T cells represent prognostic markers for NSCLC patients and might be useful for monitoring of patients’ responses to immunotherapies in future studies.

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Section: Discussionsupporting

confidence: 93%

Blood immune cell biomarkers in lung cancer

Riemann

Cwikowski

Turzer

et al. 2018

Clinical and Experimental Immunology

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“…It has been reported that T lymphocytes and their associated cytokines are abnormal in patients with cancer and are significantly involved in tumor development and progression . In the present study, we found that levels of CD8 + T cells and Th1 cells in peripheral blood of patients with NSCLC were significantly decreased, whereas Treg were increased, which were consistent with the previous findings . Nevertheless, no significant differences were observed between these cell populations and TNM stage; the reason may be due to the limited number of patients in this study.…”

Section: Discussionsupporting

confidence: 90%

“…Treg were increased, which were consistent with the previous findings. 25,26 Nevertheless, no significant differences were observed between these cell populations and TNM stage; the reason may be due to the limited number of patients in this study. Our findings suggest that the antitumor responses mediated by CD8 + T and Th1 cells may be suppressed in patients with NSCLC.…”

Section: Discussionmentioning

confidence: 64%

Long‐term prognostic significance of interleukin‐17‐producing T cells in patients with non‐small cell lung cancer

Wang

Chen

et al. 2019

Cancer Science

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The presence of interleukin (IL)‐17‐producing T cells has recently been reported in non‐small cell lung cancer (NSCLC) patients. However, the long‐term prognostic significance of these populations in NSCLC patients remains unknown. In the present study, we collected peripheral blood from 82 NSCLC patients and 22 normal healthy donors (NC). Percentages of IL‐17‐producing CD4+T (Th17), CD8+T (Tc17) and γδT cells (γδT17) were measured to determine their association with clinical outcomes and overall survival (OS) in NSCLC. All NSCLC patients were followed up until July 2018. Median follow‐up time was 13.5 months (range 1‐87 months). The 3‐ and 5‐year survival rate was 27% and 19.6%, respectively. We found that Th17 cells and γδT17 cells were significantly increased, whereas Tc17 cells were markedly decreased in patients with NSCLC compared with those in NC. In addition, Th17 cells were significantly positively associated with T helper type 1 cells (Th1), whereas γδT17 cells were significantly negatively associated with γδT + interferon (IFN)‐γ+ cells. High percentages of peripheral Tc17 cells were significantly associated with favorable 5‐year OS (P = .025), especially in patients with early TNM stage (P = .016). Furthermore, high percentages of peripheral Th17 cells were positively associated with favorable 5‐year OS in patients with late TNM stage (P = .002). However, no significant association was observed between γδT17 cells and OS, regardless of the TNM stage. In conclusion, our findings suggest that enhanced Th17 and reduced Tc17 cells in the peripheral blood could be a significant predictor of a favorable prognosis for NSCLC patients.

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“…Other studies have reported a reduction in B cells in people with cancer. Correlations between prognosis and the frequency of CD8 + naïve and memory T cells and Treg have also been reported. Our data extend these findings by showing that naïve, memory, and regulatory T cell subsets that were previously associated with disease progression in people with cancer also correlate with independent predictors of cancer progression, specifically measures of muscle function.…”

Section: Discussionmentioning

confidence: 96%

Cancer‐driven changes link T cell frequency to muscle strength in people with cancer: a pilot study

Narsale

Moya

et al. 2019

J cachexia sarcopenia muscle

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Background Tumour growth can promote the loss of muscle mass and function. This is particularly disturbing because overall survival is significantly reduced in people with weaker and smaller skeletal muscle. The risk of cancer is also greater in people who are immune deficient. Muscle wasting in mice with cancer can be inhibited by infusion of CD4 + precursor T cells that restore balanced ratios of naïve, memory, and regulatory T cells. These data are consistent with the hypothesis that stronger anti‐cancer T cell immunity leads to improved muscle mass and function. As a first step to testing this hypothesis, we determined whether levels of circulating T cell subsets correlate with levels of muscle strength in people with cancer. Methods The frequency of circulating CD4 + and CD8 + naïve, memory, and regulatory T cell subsets was quantified in 11 men with gastrointestinal cancer (aged 59.3 ± 10.1 years) and nine men without cancer (aged 60 ± 13 years), using flow cytometry. T cell marker expression was determined using real‐time PCR and western blot analyses in whole blood and peripheral blood mononuclear cells. Handgrip strength, one‐repetition maximum chest press, and knee extension tests were used to determine muscle strength. Performance was determined using a stair climb test. Body composition was determined using dual‐energy X‐ray absorptiometry scan. The Karnofsky and ECOG scales were used to assess functional impairment. Correlations between frequencies of cell subsets with strength, performance, and body composition were determined using regression analyses. Results Our data show significant correlations between (i) higher frequencies of CD8 + naïve ( P = 0.02) and effector memory ( P = 0.003) T cells and lower frequencies of CD8 + central memory T cells ( P = 0.002) with stronger handgrip strength, (ii) lower frequency of regulatory cells with greater lean mass index ( P = 0.04), (iii) lower frequency of CD8 + T cells that express CD95 with greater stair climb power ( P = 0.003), (iv) higher frequency of T cells that co‐express CD197 and CD45RA and greater one‐repetition maximum knee extension strength ( P = 0.008), and (iv) higher expression of CD4 in whole blood with greater functional impairment ( P = 0.004) in people with cancer. Conclusions We have identified significant correlations between levels of T cell populations and muscle strength, performance, and body composition in people with cancer. These data justify a follow‐up study with a larger cohort to test the validity of the findings.

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Prognostic value of circulating regulatory T cell subsets in untreated non-small cell lung cancer patients

Cited by 87 publications

References 53 publications

Blood immune cell biomarkers in lung cancer

Blood immune cell biomarkers in lung cancer

Long‐term prognostic significance of interleukin‐17‐producing T cells in patients with non‐small cell lung cancer

Cancer‐driven changes link T cell frequency to muscle strength in people with cancer: a pilot study

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