Population alterations of l-arginase- and inducible nitric oxide synthase-expressed CD11b+/CD14-/CD15+/CD33 + myeloid-derived suppressor cells and CD8+ T lymphocytes in patients with advanced-stage non-small cell lung cancer

Chien Ying Liu; Yu Min Wang; Chih Liang Wang; Po Hao Feng; How Wen Ko; Yun Hen Liu; Yi Cheng Wu; Yen Chu; Fu Tsai Chung; Chih Hsi Kuo; Kang Yun Lee; Shu Min Lin; Horng Chyuan Lin; Chun Hua Wang; Chih Teng Yu; Han Pin Kuo

doi:10.1007/s00432-009-0634-0

Population alterations of l-arginase- and inducible nitric oxide synthase-expressed CD11b⁺/CD14^-/CD15⁺/CD33 ⁺ myeloid-derived suppressor cells and CD8⁺ T lymphocytes in patients with advanced-stage non-small cell lung cancer

Chien Ying Liu^*, Yu Min Wang, Chih Liang Wang, Po Hao Feng, How Wen Ko, Yun Hen Liu, Yi Cheng Wu, Yen Chu, Fu Tsai Chung, Chih Hsi Kuo, Kang Yun Lee, Shu Min Lin, Horng Chyuan Lin, Chun Hua Wang, Chih Teng Yu, Han Pin Kuo

^*Corresponding author for this work

Chang Gung University

Research output: Contribution to journal › Journal Article › peer-review

282 Scopus citations

Abstract

Background: Immune aberrations have been demonstrated in tumorogenesis, and myeloid-derived suppressor cells (MDSC) have shown to play a pivotal role in mediating immune suppression in animal models of human tumors. In the present study, we explored the clinical relevance of CD11b⁺/CD14 ^-/CD15⁺/CD33⁺ MDSCs and the association of MDSCs with CD8⁺ cytotoxic T lymphocytes in patients with non-small-cell lung cancer (NSCLC). Patients and methods: The population of CD11b⁺/CD14^- cells in peripheral blood mononuclear cells (PBMNC) was determined in 173 patients with NSCLC and 42 control subjects. The expression of CD15, CD33, IL-4R, INF-γR, iNOS and l-arginase were analyzed. Cocultures with CD8⁺ T lymphocytes and Jurkat cells were developed to determine the impact of MDSCs on the expression of CD3ζ of CD8⁺ T lymphocytes. Results: Patients with treatment-naïve, advanced-stage NSCLC (n = 87) had an increased subpopulation of CD11b ⁺/CD14^-/CD15⁺/CD33⁺ cells in the PBMNCs with characteristics of MDSCs (P < 0.0001). The CD11b ⁺/CD14^- cells in PBMNC also express IL-4R and INF-γR and can suppress CD3ζ expression in CD8⁺ T lymphocytes. The subpopulation of CD11b⁺/CD14^- cells in PBMNC was decreased in the advanced-stage NSCLC patients who had responsiveness to chemotherapy (n = 41, P < 0.0001) and in the early-stage NSCLC patients after removal of tumor (n = 8, P = 0.0391). Notably, a negative association existed between the population of CD11b⁺/CD14^- cells in PBMNC and the frequency of CD8⁺ T lymphocytes (n = 48, r = -0.3141, P = 0.0297). Conclusions: Our study provided evidence of an increased pool of CD11b ⁺/CD14^-/CD15⁺/CD33⁺ MDSCs in the peripheral blood of NSCLC patients. For the suppressive effect of the cells on CD8⁺ T lymphocytes, these findings suggest the important role of the CD11b⁺/CD14^-/CD15⁺/CD33⁺ MDSCs in mediating immunosuppression in NSCLC.

Original language	English
Pages (from-to)	35-45
Number of pages	11
Journal	Journal of Cancer Research and Clinical Oncology
Volume	136
Issue number	1
DOIs	https://doi.org/10.1007/s00432-009-0634-0
State	Published - 01 2010

Keywords

Immunosuppression
Myeloid-derived suppressor cells (MDSC)
Non-small-cell lung cancer (NSCLC)
T lymphocytes

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Liu, C. Y., Wang, Y. M., Wang, C. L., Feng, P. H., Ko, H. W., Liu, Y. H., Wu, Y. C., Chu, Y., Chung, F. T., Kuo, C. H., Lee, K. Y., Lin, S. M., Lin, H. C., Wang, C. H., Yu, C. T., & Kuo, H. P. (2010). Population alterations of l-arginase- and inducible nitric oxide synthase-expressed CD11b⁺/CD14^-/CD15⁺/CD33 ⁺ myeloid-derived suppressor cells and CD8⁺ T lymphocytes in patients with advanced-stage non-small cell lung cancer. Journal of Cancer Research and Clinical Oncology, 136(1), 35-45. https://doi.org/10.1007/s00432-009-0634-0

Liu, Chien Ying ; Wang, Yu Min ; Wang, Chih Liang et al. / Population alterations of l-arginase- and inducible nitric oxide synthase-expressed CD11b⁺/CD14^-/CD15⁺/CD33 ⁺ myeloid-derived suppressor cells and CD8⁺ T lymphocytes in patients with advanced-stage non-small cell lung cancer. In: Journal of Cancer Research and Clinical Oncology. 2010 ; Vol. 136, No. 1. pp. 35-45.

@article{fed562c9020343cdbad6d384296f7e8b,

title = "Population alterations of l-arginase- and inducible nitric oxide synthase-expressed CD11b+/CD14-/CD15+/CD33 + myeloid-derived suppressor cells and CD8+ T lymphocytes in patients with advanced-stage non-small cell lung cancer",

abstract = "Background: Immune aberrations have been demonstrated in tumorogenesis, and myeloid-derived suppressor cells (MDSC) have shown to play a pivotal role in mediating immune suppression in animal models of human tumors. In the present study, we explored the clinical relevance of CD11b+/CD14 -/CD15+/CD33+ MDSCs and the association of MDSCs with CD8+ cytotoxic T lymphocytes in patients with non-small-cell lung cancer (NSCLC). Patients and methods: The population of CD11b+/CD14- cells in peripheral blood mononuclear cells (PBMNC) was determined in 173 patients with NSCLC and 42 control subjects. The expression of CD15, CD33, IL-4R, INF-γR, iNOS and l-arginase were analyzed. Cocultures with CD8+ T lymphocytes and Jurkat cells were developed to determine the impact of MDSCs on the expression of CD3ζ of CD8+ T lymphocytes. Results: Patients with treatment-na{\"i}ve, advanced-stage NSCLC (n = 87) had an increased subpopulation of CD11b +/CD14-/CD15+/CD33+ cells in the PBMNCs with characteristics of MDSCs (P < 0.0001). The CD11b +/CD14- cells in PBMNC also express IL-4R and INF-γR and can suppress CD3ζ expression in CD8+ T lymphocytes. The subpopulation of CD11b+/CD14- cells in PBMNC was decreased in the advanced-stage NSCLC patients who had responsiveness to chemotherapy (n = 41, P < 0.0001) and in the early-stage NSCLC patients after removal of tumor (n = 8, P = 0.0391). Notably, a negative association existed between the population of CD11b+/CD14- cells in PBMNC and the frequency of CD8+ T lymphocytes (n = 48, r = -0.3141, P = 0.0297). Conclusions: Our study provided evidence of an increased pool of CD11b +/CD14-/CD15+/CD33+ MDSCs in the peripheral blood of NSCLC patients. For the suppressive effect of the cells on CD8+ T lymphocytes, these findings suggest the important role of the CD11b+/CD14-/CD15+/CD33+ MDSCs in mediating immunosuppression in NSCLC.",

keywords = "Immunosuppression, Myeloid-derived suppressor cells (MDSC), Non-small-cell lung cancer (NSCLC), T lymphocytes",

author = "Liu, {Chien Ying} and Wang, {Yu Min} and Wang, {Chih Liang} and Feng, {Po Hao} and Ko, {How Wen} and Liu, {Yun Hen} and Wu, {Yi Cheng} and Yen Chu and Chung, {Fu Tsai} and Kuo, {Chih Hsi} and Lee, {Kang Yun} and Lin, {Shu Min} and Lin, {Horng Chyuan} and Wang, {Chun Hua} and Yu, {Chih Teng} and Kuo, {Han Pin}",

year = "2010",

month = jan,

doi = "10.1007/s00432-009-0634-0",

language = "英语",

volume = "136",

pages = "35--45",

journal = "Journal of Cancer Research and Clinical Oncology",

issn = "0171-5216",

publisher = "Springer Science and Business Media Deutschland GmbH",

number = "1",

}

Liu, CY, Wang, YM, Wang, CL, Feng, PH, Ko, HW, Liu, YH, Wu, YC, Chu, Y, Chung, FT, Kuo, CH, Lee, KY, Lin, SM, Lin, HC, Wang, CH, Yu, CT & Kuo, HP 2010, 'Population alterations of l-arginase- and inducible nitric oxide synthase-expressed CD11b⁺/CD14^-/CD15⁺/CD33 ⁺ myeloid-derived suppressor cells and CD8⁺ T lymphocytes in patients with advanced-stage non-small cell lung cancer', Journal of Cancer Research and Clinical Oncology, vol. 136, no. 1, pp. 35-45. https://doi.org/10.1007/s00432-009-0634-0

Population alterations of l-arginase- and inducible nitric oxide synthase-expressed CD11b⁺/CD14^-/CD15⁺/CD33 ⁺ myeloid-derived suppressor cells and CD8⁺ T lymphocytes in patients with advanced-stage non-small cell lung cancer. / Liu, Chien Ying; Wang, Yu Min; Wang, Chih Liang et al.
In: Journal of Cancer Research and Clinical Oncology, Vol. 136, No. 1, 01.2010, p. 35-45.

Research output: Contribution to journal › Journal Article › peer-review

TY - JOUR

T1 - Population alterations of l-arginase- and inducible nitric oxide synthase-expressed CD11b+/CD14-/CD15+/CD33 + myeloid-derived suppressor cells and CD8+ T lymphocytes in patients with advanced-stage non-small cell lung cancer

AU - Liu, Chien Ying

AU - Wang, Yu Min

AU - Wang, Chih Liang

AU - Feng, Po Hao

AU - Ko, How Wen

AU - Liu, Yun Hen

AU - Wu, Yi Cheng

AU - Chu, Yen

AU - Chung, Fu Tsai

AU - Kuo, Chih Hsi

AU - Lee, Kang Yun

AU - Lin, Shu Min

AU - Lin, Horng Chyuan

AU - Wang, Chun Hua

AU - Yu, Chih Teng

AU - Kuo, Han Pin

PY - 2010/1

Y1 - 2010/1

N2 - Background: Immune aberrations have been demonstrated in tumorogenesis, and myeloid-derived suppressor cells (MDSC) have shown to play a pivotal role in mediating immune suppression in animal models of human tumors. In the present study, we explored the clinical relevance of CD11b+/CD14 -/CD15+/CD33+ MDSCs and the association of MDSCs with CD8+ cytotoxic T lymphocytes in patients with non-small-cell lung cancer (NSCLC). Patients and methods: The population of CD11b+/CD14- cells in peripheral blood mononuclear cells (PBMNC) was determined in 173 patients with NSCLC and 42 control subjects. The expression of CD15, CD33, IL-4R, INF-γR, iNOS and l-arginase were analyzed. Cocultures with CD8+ T lymphocytes and Jurkat cells were developed to determine the impact of MDSCs on the expression of CD3ζ of CD8+ T lymphocytes. Results: Patients with treatment-naïve, advanced-stage NSCLC (n = 87) had an increased subpopulation of CD11b +/CD14-/CD15+/CD33+ cells in the PBMNCs with characteristics of MDSCs (P < 0.0001). The CD11b +/CD14- cells in PBMNC also express IL-4R and INF-γR and can suppress CD3ζ expression in CD8+ T lymphocytes. The subpopulation of CD11b+/CD14- cells in PBMNC was decreased in the advanced-stage NSCLC patients who had responsiveness to chemotherapy (n = 41, P < 0.0001) and in the early-stage NSCLC patients after removal of tumor (n = 8, P = 0.0391). Notably, a negative association existed between the population of CD11b+/CD14- cells in PBMNC and the frequency of CD8+ T lymphocytes (n = 48, r = -0.3141, P = 0.0297). Conclusions: Our study provided evidence of an increased pool of CD11b +/CD14-/CD15+/CD33+ MDSCs in the peripheral blood of NSCLC patients. For the suppressive effect of the cells on CD8+ T lymphocytes, these findings suggest the important role of the CD11b+/CD14-/CD15+/CD33+ MDSCs in mediating immunosuppression in NSCLC.

AB - Background: Immune aberrations have been demonstrated in tumorogenesis, and myeloid-derived suppressor cells (MDSC) have shown to play a pivotal role in mediating immune suppression in animal models of human tumors. In the present study, we explored the clinical relevance of CD11b+/CD14 -/CD15+/CD33+ MDSCs and the association of MDSCs with CD8+ cytotoxic T lymphocytes in patients with non-small-cell lung cancer (NSCLC). Patients and methods: The population of CD11b+/CD14- cells in peripheral blood mononuclear cells (PBMNC) was determined in 173 patients with NSCLC and 42 control subjects. The expression of CD15, CD33, IL-4R, INF-γR, iNOS and l-arginase were analyzed. Cocultures with CD8+ T lymphocytes and Jurkat cells were developed to determine the impact of MDSCs on the expression of CD3ζ of CD8+ T lymphocytes. Results: Patients with treatment-naïve, advanced-stage NSCLC (n = 87) had an increased subpopulation of CD11b +/CD14-/CD15+/CD33+ cells in the PBMNCs with characteristics of MDSCs (P < 0.0001). The CD11b +/CD14- cells in PBMNC also express IL-4R and INF-γR and can suppress CD3ζ expression in CD8+ T lymphocytes. The subpopulation of CD11b+/CD14- cells in PBMNC was decreased in the advanced-stage NSCLC patients who had responsiveness to chemotherapy (n = 41, P < 0.0001) and in the early-stage NSCLC patients after removal of tumor (n = 8, P = 0.0391). Notably, a negative association existed between the population of CD11b+/CD14- cells in PBMNC and the frequency of CD8+ T lymphocytes (n = 48, r = -0.3141, P = 0.0297). Conclusions: Our study provided evidence of an increased pool of CD11b +/CD14-/CD15+/CD33+ MDSCs in the peripheral blood of NSCLC patients. For the suppressive effect of the cells on CD8+ T lymphocytes, these findings suggest the important role of the CD11b+/CD14-/CD15+/CD33+ MDSCs in mediating immunosuppression in NSCLC.

KW - Immunosuppression

KW - Myeloid-derived suppressor cells (MDSC)

KW - Non-small-cell lung cancer (NSCLC)

KW - T lymphocytes

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Liu CY, Wang YM, Wang CL, Feng PH, Ko HW, Liu YH et al. Population alterations of l-arginase- and inducible nitric oxide synthase-expressed CD11b⁺/CD14^-/CD15⁺/CD33 ⁺ myeloid-derived suppressor cells and CD8⁺ T lymphocytes in patients with advanced-stage non-small cell lung cancer. Journal of Cancer Research and Clinical Oncology. 2010 Jan;136(1):35-45. doi: 10.1007/s00432-009-0634-0