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Immunophenotyping of patients with oral squamous cell carcinoma in peripheral blood and associated tumor tissue

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Tumor Biology

Abstract

The immune system is important for elimination of cancer cells. Tumors including oral squamous cell carcinoma (OSCC) are capable of escaping detection by host immune cells through apoptotic depletion of tumor-infiltrating lymphocytes (TILs). Circulating peripheral blood lymphocytes (PBLs) and corresponding TILs of tumor specimen were evaluated before and after curative tumor resection (n = 30) compared with PBLs of controls (n = 87). PBLs were characterized for the total number of T cells (CD3+), T helper cells (Th, CD3+/CD4+), regulatory T cells (Treg, CD4+/CD25+/CD127low), cytotoxic T cells (Tc, CD3+/CD8+), activated T cells (CD3+/HLA-DR+), and natural killer (NK) cells (CD3−/CD16+/CD56+). In tumor tissue, the prevalence of CD3+, CD4+, and CD8+ TILs was assessed using immunohistochemistry, whereas the incidence of apoptosis was assessed using terminal deoxynucleotidyl transferase deoxyuridinetriphosphate nick-end labeling (TUNEL) assay. In PBLs of pretreated OSCC patients, a highly significant decrease in total number of T cells (p = 0.0001), Th cells (p < 0.0001), Treg cells (p < 0.0001), Tc cells (p < 0.0001), and NK cells (p = 0.0037) were found compared with controls. Decreased PBLs of OSCC patients were correlated with decreased numbers of corresponding TILs, which were associated with increased detection of apoptosis in the tumor tissue. Compared with the controls, the total number of T cells remained unchanged after surgery but the total number of NK cells significantly increased. Standardized immunophenotyping of OSCC may help to identify patients likely to benefit from cancer immunotherapy strategies and/or chemoradiation. Finally, future attempts to enhance an effective tumor-reactive immune response by immunotherapy or vaccination should be made by promoting tumor-specific Th and/or Tc cell/NK cell responses.

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Abbreviations

PBLs:

Peripheral blood lymphocytes

TILs:

Tumor-infiltrating lymphocytes

OSCC:

Oral squamous cell carcinoma

Th:

T helper cells

Treg:

Regulatory T cells

Tc:

Cytotoxic T cells

NK:

Natural killer cells

IHC:

Immunohistochemistry

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Acknowledgments

We thank biovis’ Diagnostik MVZ especially Melanie Hügen and Martina Thümmler for the technical support.

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    Authors and Affiliations

    1. Department of Oral and Maxillofacial Surgery, University Hospital Tübingen, Osianderstrasse 2-8, 72076, Tübingen, Germany

      Martin Grimm, Adelheid Munz & Siegmar Reinert

    2. Zyagnum AG, Reißstraße 1a, 64319, Pfungstadt, Germany

      Oliver Feyen

    3. biovis’ Diagnostik MVZ, Justus-Staudt-Straße 2, 65555, Limburg an der Lahn, Germany

      Heiko Hofmann

    4. Cancer Research Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA

      Peter Teriete

    5. Department of Pathology, University Hospital Tübingen, Liebermeisterstrasse 8, 72076, Tübingen, Germany

      Thorsten Biegner

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    1. Martin Grimm
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    Correspondence to Martin Grimm.

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    Authors’ contributions

    MG and OF conceived the study, performed the coordination, and drafted the manuscript. OF performed flow cytometric analysis. TB and AM analyzed histopathological specimen and carried out immunohistochemistry studies. MG and PT carried out the data collection and performed the statistical analyses. SR performed surgical treatment, after care of the patients, and drafted the manuscript. All authors read and approved the final manuscript.

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    Written informed consent to participate was obtained prospectively from all patients (Ethics Committee Tübingen, Germany, approval number: 562-2013BO2).

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    Martin Grimm and Oliver Feyen contributed equally to this work.

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    Grimm, M., Feyen, O., Hofmann, H. et al. Immunophenotyping of patients with oral squamous cell carcinoma in peripheral blood and associated tumor tissue. Tumor Biol. 37, 3807–3816 (2016). https://doi.org/10.1007/s13277-015-4224-2

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    • DOI: https://doi.org/10.1007/s13277-015-4224-2

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