Increase of regulatory T cells in metastatic stage and CTLA-4 over expression in lymphocytes of patients with non-small cell lung cancer (NSCLC)

Erfani, Nasrollah; Mehrabadi, Shayesteh Mofakhami; Ghayumi, Mohammad Ali; Haghshenas, Mohammad Reza; Mojtahedi, Zahra; Ghaderi, Abbas; Amani, Davar

doi:10.1016/j.lungcan.2012.04.011

Cited by 134 publications

(89 citation statements)

References 38 publications

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“…Patients with NSCLC also had an increased percentage of Tregs than controls. The proportion of Tregs increased in an advanced stage of NSCLC (7). Moreover, pleural fluid from benign disease contained mainly CD8 þ T cells, whereas MPEs included mainly CD4 þ T cells (8).…”

Section: Introductionmentioning

confidence: 96%

miR141–CXCL1–CXCR2 Signaling–Induced Treg Recruitment Regulates Metastases and Survival of Non–Small Cell Lung Cancer

Tang

et al. 2014

Molecular Cancer Therapeutics

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Patients with non-small cell lung cancer (NSCLC) with malignant pleural effusion (MPE) have a short median survival time and increased regulatory T cells (Treg). However, it is unclear whether some specific factors in MPE are involved in Treg recruitment in the progression of NSCLC. Here, we found that Treg population was increased in MPE and inversely correlated with patient survival (P < 0.001). Increased level of CXCL1 in MPE was associated with recruitment of Tregs (P < 0.01). Moreover, miR141 regulated expression of CXCL1 in lung cancer cells, whereas the luciferase test confirmed that CXCL1 is a target of miR141. Chemotaxis assay showed that the miR141-CXCL1-CXCR2 pathway regulates migration of Tregs into MPE. Furthermore, miR141 significantly inhibited tumor growth and metastasis in an immunecompetent mouse model. This suppressive function was mediated by the CXCL1-CXCR2 pathway and recruitment of Tregs. Our study uncovered a causative link between microRNA and development of MPE. Mechanistically, decreased expressions of miR141, associated with the survival of patients with NSCLC with MPE, resulted in the increased production of CXCL1 and recruitment of Tregs to promote immune escape of tumor. Mol Cancer Ther; 13(12); 3152-62. Ó2014 AACR.

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Section: Introductionmentioning

confidence: 96%

miR141–CXCL1–CXCR2 Signaling–Induced Treg Recruitment Regulates Metastases and Survival of Non–Small Cell Lung Cancer

Tang

et al. 2014

Molecular Cancer Therapeutics

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“…Treg cells also constitutively express the transcription factor, Foxp3, and some studies have accordingly used this as a marker of Tregs in addition to (or instead of) assessing CD25 and CD4 expression. Higher levels of CD4+ CD25+ Treg cells have been observed in the peripheral blood of patients with NSCLC compared with healthy controls [28][29][30][31]. In some studies, the proportion of Treg cells (or, in one case, a subpopulation of Treg cells which also expressed CD13) was found to increase with NSCLC stage [31,32], but decreased on surgical removal of tumors [32].…”

Section: Rationale For Immunotherapy In Nsclcmentioning

confidence: 99%

“…Higher levels of CD4+ CD25+ Treg cells have been observed in the peripheral blood of patients with NSCLC compared with healthy controls [28][29][30][31]. In some studies, the proportion of Treg cells (or, in one case, a subpopulation of Treg cells which also expressed CD13) was found to increase with NSCLC stage [31,32], but decreased on surgical removal of tumors [32]. The proportion of Treg cells was also significantly higher in metastatic than non-metastatic stages [31], and another study found higher Foxp3 expression in metastatic lymph nodes than in non-metastatic nodes [30].…”

Section: Rationale For Immunotherapy In Nsclcmentioning

confidence: 99%

“…In some studies, the proportion of Treg cells (or, in one case, a subpopulation of Treg cells which also expressed CD13) was found to increase with NSCLC stage [31,32], but decreased on surgical removal of tumors [32]. The proportion of Treg cells was also significantly higher in metastatic than non-metastatic stages [31], and another study found higher Foxp3 expression in metastatic lymph nodes than in non-metastatic nodes [30]. In a cohort of patients with stage I NSCLC, a higher ratio of Treg cells to tumor-infiltrating T cell lymphocytes was linked with significantly increased risk of disease recurrence [33].…”

Section: Rationale For Immunotherapy In Nsclcmentioning

confidence: 99%

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Targeting the immune system for management of NSCLC: the revival?

Reck

Vansteenkiste

Brahmer

2013

Curr Respir Care Rep

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Immunotherapy, based on increasing knowledge of the mechanisms of immune-mediated elimination of tumor cells, is a new approach to lung cancer therapy. This paper reviews clinical experience of two types of immunotherapy for lung cancer. In the first approach antigen-independent immunomodulatory therapy is used to target crucial immune checkpoints. This strategy includes use of ipilimumab-to block the interaction of cytotoxic T-lymphocyte antigen-4 with CD80 and/or CD86, thereby enhancing T-cell proliferation-and the fully human monoclonal antibodies BMS-936558 and BMS-936559-to target the programmed cell death protein 1 signaling pathway, thereby enhancing T-cell proliferation, cytokine secretion, and cytolysis of target cells. The second approach is antigen-specific cancer immunotherapy, including vaccines against melanoma-associated antigen 3, mucinous glycoprotein-1, transforming growth factor-beta 2, epidermal growth factor, and, less specifically, whole-tumor cell extracts. An overview of the clinical data from these strategies is presented, with discussion of questions and issues that remain unanswered.

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“…The expansion and activation of certain T-cell populations, including cytotoxic CD8 + T cells, has been reported to be beneficial for the recognition and elimination of cancer cells (28,29). By contrast, the expansion of regulatory T cells may be harmful, as these T cells protect cancer cells by suppressing tumor-specific CD8 + cytotoxic T cells (30)(31)(32)(33). Therefore, it is important to quantitatively characterize the T-cell receptor (TCR) repertoires of patients with cancer prior to and following immunotherapy, including cancer vaccine treatment, to improve the understanding of the molecular mechanism underlying treatment efficacy.…”

Section: Introductionmentioning

confidence: 99%

Quantitative analysis and clonal characterization of T-cell receptor β repertoires in patients with advanced non-small cell lung cancer treated with cancer vaccine

et al. 2017

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Increase of regulatory T cells in metastatic stage and CTLA-4 over expression in lymphocytes of patients with non-small cell lung cancer (NSCLC)

Cited by 134 publications

References 38 publications

miR141–CXCL1–CXCR2 Signaling–Induced Treg Recruitment Regulates Metastases and Survival of Non–Small Cell Lung Cancer

miR141–CXCL1–CXCR2 Signaling–Induced Treg Recruitment Regulates Metastases and Survival of Non–Small Cell Lung Cancer

Targeting the immune system for management of NSCLC: the revival?

Quantitative analysis and clonal characterization of T-cell receptor β repertoires in patients with advanced non-small cell lung cancer treated with cancer vaccine

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