Changes of CD4+CD25+FOXP3+ and CD8+CD28− regulatory T cells in non-small cell lung cancer patients undergoing surgery

Chen, Cheng; Chen, Dongdong; Zhang, Yongkui; Chen, Zhijun; Zhu, Wenxiu; Zhang, Binjie; Wang, Zhaoye; Le, Hanh

doi:10.1016/j.intimp.2013.12.004

Cited by 65 publications

(54 citation statements)

References 32 publications

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“…35 In another study in NSCLC patients, circulating Treg levels were also reduced 1–3 months after pneumectomy or lobectomy. 36 In contrast to these studies, in our study the Treg levels in blood were not significantly different between the P/D and no P/D groups three months after surgery. However, we analyzed only a limited number of patients, we could not study the effect of P/D on Tregs within the TME, preoperative data were not available and the P/D patients were at least three months after P/D.…”

Section: Discussioncontrasting

confidence: 96%

Low-dose cyclophosphamide depletes circulating naïve and activated regulatory T cells in malignant pleural mesothelioma patients synergistically treated with dendritic cell-based immunotherapy

et al. 2018

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Rationale: Regulatory T cells (Treg) play a pivotal role in the immunosuppressive tumor micro-environment in cancer, including mesothelioma. Recently, the combination of autologous tumor lysate-pulsed dendritic cells (DC) and metronomic cyclophosphamide (mCTX) was reported as a feasible and well-tolerated treatment in malignant pleural mesothelioma patients and further as a method to reduce circulating Tregs.Objectives: The aim of this study was to establish the immunological effects of mCTX alone and in combination with DC-based immunotherapy on circulating Treg and other T cell subsets in mesothelioma patients.Methods: Ten patients received mCTX and DC-based immunotherapy after chemotherapy (n = 5) or chemotherapy and debulking surgery (n = 5). Peripheral blood mononuclear cells before, during and after treatment were analyzed for various Treg and other lymphocyte subsets by flow cytometry.Results: After one week treatment with mCTX, both activated FoxP3hi and naïve CD45RA+ Tregs were effectively decreased in all patients. In addition, a shift from naïve and central memory towards effector memory and effector T cells was observed. Survival analysis showed that overall Treg levels before treatment were not correlated with survival, however, nTreg levels before treatment were positively correlated with survival. After completion of mCTX and DC-based immunotherapy treatment, all cell subsets returned to baseline levels, except for the proportions of proliferating EM CD8 T cells, which increased.Conclusions: mCTX treatment effectively reduced the proportions of circulating Tregs, both aTregs and nTregs, thereby favoring EM T cell subsets in mesothelioma patients. Interestingly, baseline levels of nTregs were positively correlated to overall survival upon complete treatment.

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Section: Discussioncontrasting

confidence: 96%

Low-dose cyclophosphamide depletes circulating naïve and activated regulatory T cells in malignant pleural mesothelioma patients synergistically treated with dendritic cell-based immunotherapy

et al. 2018

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“…This may be due to the predominant use of lung cancer patients with early stage cancer: In previous studies, the percentages of T reg cells in patients with early stage cancer increased marginally or did not increase at all postoperatively [preoperative vs. postoperative: Stage I (2.34 vs. 1.77%), stage II (2.72 vs. 1.94%)], whereas the postoperative T reg percentage in patients with advanced stage (III+IV) cancer remained high (preoperative vs. postoperative: 1.61 vs. 3.52%) (29).…”

Section: Discussionmentioning

confidence: 98%

Effects of transcutaneous acupoint electrical stimulation on the imbalance of Th1, Th2, Th17 and Treg cells following thoracotomy of patients with lung cancer

Wang

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. An imbalance in the various T lymphocytes, including T-helper (Th) 1 , Th 2 and Th 17 cells, and regulatory T (T reg ) cells, has been associated with immune dysfunction, and may occur following thoracotomy of patients with lung cancer. The use of transcutaneous acupoint electrical stimulation (TAES) has previously been demonstrated to exert immunoregulatory effects; therefore, the present study aimed to evaluate whether TAES was able to attenuate postoperative immune suppression in patients with lung cancer. Thoracic surgical patients with lung cancer (n=27) underwent TAES (frequency, 2/100 Hz; intensity, 4-12 mA) at the bilateral large intestine 4, pericardium 6, small intestine 3 and San Jiao 6 acupuncture points for 30 min, prior to incision, and at 20, 44, 68, 92 and 116 h following thoracotomy. The number of Th 1 , Th 2 , Th 17 and T reg cells, and the protein and mRNA expression levels of related cytokines were measured by flow cytometry, ELISA and polymerase chain reaction, respectively. The balance of Th 1 , Th 2 , Th 17 and T reg cells in the peripheral blood of patients with lung cancer was disrupted following thoracotomy. TAES administration increased the percentage of Th 1 and Th 17 cells, the protein expression levels of interleukin (IL)-2 and interferon-γ, the mRNA expression levels of T-bet and RAR-related orphan receptor-γt, and decreased the percentage of Th 2 cells, IL-10 protein expression levels, and GATA binding protein 3 mRNA expression levels. The results of the present study demonstrated that TAES was able to partially attenuate the postoperative immune depression of patients with lung cancer, by regulating the balance of Th 1 , Th 2 , Th 17 and T reg cells, and the expression levels of related cytokines and transcription factors; therefore, TAES may be considered to be a promising strategy for treating postoperative immune dysfunction in patients with lung cancer.

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“…However, the balance between T-effector and T-regs in tumors is known to determine the functional outcome of immune responses [36], and both Th1/Treg and CD8/Treg ratios were lower in TT than in DNTT. Although the precise mechanism of Tregs-mediated suppression has yet to be fully elucidated [37–39], at least part of the immunosuppressive effect may be could be exerted by CD39. This ectoenzyme serves as an integral component of the suppressive machinery of Tregs, inactivating and converting extracellular ATP into adenosine and allowing the immune escape of tumors [40–42].…”

Section: Discussionmentioning

confidence: 99%

Progressive changes in composition of lymphocytes in lung tissues from patients with non-small-cell lung cancer

et al. 2016

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Immune cell infiltration is a common feature of many human solid tumors. Innate and adaptative immune systems contribute to tumor immunosurveillance. We investigated whether tumors evade immune surveillance by inducing states of tolerance and/or through the inability of some immune subpopulations to effectively penetrate tumor nests. Immunohistochemistry and flow cytometry analysis were used to study the composition and distribution of immune subpopulations in samples of peripheral blood, tumor tissue (TT), adjacent tumor tissue (ATT), distant non-tumor tissue (DNTT), cancer nests, cancer stroma, and invasive margin in 61 non-small-cell lung cancer (NSCLC) patients. A significantly higher percentage of T and B cells and significantly lower percentage of NK cells were detected in TT than in DNTT. Memory T cells (CD4+CD45RO+, CD8+CD45RO+) and activated T cells (CD8+DR+) were more prevalent in TT. Alongside this immune activation, the percentage of T cells with immunosuppressive activity was higher in TT than in DNTT. B- cells were practically non-existent in tumor nests and were preferentially located in the invasive margin. The dominant NK cell phenotype in peripheral blood and DNTT was the cytotoxic phenotype (CD56+ CD16+), while the presence of these cells was significantly decreased in ATT and further decreased in TT. Finally, the immunologic response differed between adenocarcinoma and squamous cell carcinoma and according to the tumor differentiation grade. These findings on the infiltration of innate and adaptative immune cells into tumors contribute to a more complete picture of the immune reaction in NSCLC.

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Changes of CD4+CD25+FOXP3+ and CD8+CD28− regulatory T cells in non-small cell lung cancer patients undergoing surgery

Cited by 65 publications

References 32 publications

Low-dose cyclophosphamide depletes circulating naïve and activated regulatory T cells in malignant pleural mesothelioma patients synergistically treated with dendritic cell-based immunotherapy

Low-dose cyclophosphamide depletes circulating naïve and activated regulatory T cells in malignant pleural mesothelioma patients synergistically treated with dendritic cell-based immunotherapy

Effects of transcutaneous acupoint electrical stimulation on the imbalance of Th1, Th2, Th17 and Treg cells following thoracotomy of patients with lung cancer

Progressive changes in composition of lymphocytes in lung tissues from patients with non-small-cell lung cancer

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