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Peripheral CD8+ T cell proliferation is prognostic for patients with advanced thoracic malignancies

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Abstract

There is a complex interplay between the immune system and a developing tumor that is manifest in the way that the balance of T cell subsets in the local tumor environment reflects clinical outcome. Tumor infiltration by CD8+ T cells and regulatory T cells (Treg) is associated with improved and reduced survival, respectively, in many cancer types. However, little is known of the prognostic value of immunological parameters measured in peripheral blood. In this study, peripheral CD8+ T cells and Treg from 43 patients with malignant mesothelioma or advanced non-small-cell lung cancer scheduled to commence palliative chemotherapy were assessed by flow cytometry and evaluated for association with patient survival. Patients had a higher proportion of peripheral Treg, proliferating CD8+ T cells and CD8+ T cells with an activated effector phenotype compared with age-matched healthy controls. Higher proportions of Treg and proliferating CD8+ T cells were both associated with poor survival in univariate analyses (hazard ratio [HR] 3.81, 95 % CI 1.69–8.57; p < 0.01 and HR 2.86, 95 % CI 1.26–6.50; p < 0.05, respectively). CD8+ T cell proliferation was independently predictive of reduced survival in multivariate analysis (HR 2.58, 95 % CI 1.01–6.61; p < 0.05). These findings suggest that peripheral CD8+ T cell proliferation can be a useful prognostic marker in patients with thoracic malignancies planned for palliative chemotherapy.

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Abbreviations

CTL:

Cytotoxic lymphocyte

ECOG:

Eastern Cooperative Oncology Group

HR:

Hazard ratio

MM:

Malignant mesothelioma

NSCLC:

Non-small-cell lung cancer

TAA:

Tumor-associated antigen

TTP:

Time to progression

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Acknowledgments

This study was supported by the National Health and Medical Research Council (NHMRC) and the National Centre for Asbestos Related Diseases (NCARD). MJM was funded by an International Postgraduate Research Scholarship. We thank Professors Bruce Robinson, Michael Millward, Michael Byrne and Dr Arman Hasani for their assistance. Flow cytometry was conducted at the Australian Microscopy & Microanalysis Research Facility at the Centre for Microscopy, Characterisation & Analysis, The University of Western Australia, and we thank Dr Kathy Heel and Tracey Lee-Pullen for their technical support. The antigen-specific T cell expansion method used was based on a protocol kindly provided by Professor Jonathan Cebon, Ludwig Institute for Cancer Research, Victoria, Australia.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. School of Medicine and Pharmacology, The University of Western Australia, M503, 35 Stirling Highway, Crawley, WA, 6009, Australia

    Melanie J. McCoy, Anna K. Nowak, Robbert G. van der Most, Ian M. Dick & Richard A. Lake

  2. National Centre for Asbestos Related Diseases, Nedlands, Australia

    Melanie J. McCoy, Anna K. Nowak, Robbert G. van der Most, Ian M. Dick & Richard A. Lake

  3. Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, WA, 6009, Australia

    Melanie J. McCoy & Anna K. Nowak

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McCoy, M.J., Nowak, A.K., van der Most, R.G. et al. Peripheral CD8+ T cell proliferation is prognostic for patients with advanced thoracic malignancies. Cancer Immunol Immunother 62, 529–539 (2013). https://doi.org/10.1007/s00262-012-1360-z

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