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Lung T-cell subset composition at the time of surgical resection is a prognostic indicator in non-small cell lung cancer

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Abstract

NSCLC arises in the complex environment of chronic inflammation. Depending on lung immune polarization, infiltrating immune cells may either promote or suppress tumor growth. Despite the importance of the immune microenvironment, current staging techniques for NSCLC do not take into consideration the immune milieu in which the neoplasms arise. T-cell subset content was compared between paired tumor-bearing and contralateral lungs, patient and control peripheral blood. The relationship between T-cell subset distribution and survival were evaluated. CD4 and CD8+ T cells were subsetted by CD45RA/CD27 and analyzed for expression of activation, adhesion, and homing markers. Strikingly, T-cell content was indistinguishable between lungs. Compared with peripheral blood, naïve CD4 and CD8 T cells were rare in BAL. CD4+ BAL T cells showed increased CD95 (higher apoptotic potential) and CD103 expression (epithelial adhesion), but decreased CD38 (activation) and CCR7 expression (lymph node homing). CD8+ BAL T cells showed increased CD103 expression and decreased CD28 expression (co-stimulation). Differences in CD28, CD95, and CCR7 expression were more pronounced within memory cells, while differences in CD4+ CD103 expression were more prominent in effector/memory cells. Of these populations, the absence of lung CD4 T cells with an effector-like phenotype (CD45RA+/CD27−) emerged as a predictor of favorable outcome. Patients with a low proportion (≤0.44%) had 90% 5-year survival (n = 10, median survival 2,343 days), compared with 0% (n = 9, median survival 516 days) of patients with a higher proportion. Further study is required to confirm this association prospectively and define the function of this subpopulation.

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Acknowledgments

The authors would like to thank Drs. Theresa Whiteside and Jill Siegfried for their careful reading and critique of this manuscript. This work was supported by the Heart Lung and Esophageal Institute of the University of Pittsburgh Medical Center, and the University of Pittsburgh Lung Cancer SPORE: NCI P50-CA90440.

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Authors and Affiliations

  1. University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    T. A. Zikos

  2. Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    A. D. Donnenberg

  3. Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA

    A. D. Donnenberg

  4. Department of Infectious Disease and Microbiology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA

    A. D. Donnenberg

  5. Hillman Cancer Research Center, University of Pittsburgh, 2.42, 5117 Centre Avenue, Pittsburgh, PA, 15213, USA

    A. D. Donnenberg & V. S. Donnenberg

  6. Department of Cardiothoracic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    R. J. Landreneau, J. D. Luketich & V. S. Donnenberg

  7. University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA

    V. S. Donnenberg

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  1. T. A. Zikos
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  2. A. D. Donnenberg
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  3. R. J. Landreneau
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  4. J. D. Luketich
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  5. V. S. Donnenberg
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Correspondence to A. D. Donnenberg or V. S. Donnenberg.

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Zikos, T.A., Donnenberg, A.D., Landreneau, R.J. et al. Lung T-cell subset composition at the time of surgical resection is a prognostic indicator in non-small cell lung cancer. Cancer Immunol Immunother 60, 819–827 (2011). https://doi.org/10.1007/s00262-011-0996-4

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