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Tumor Biology

, Volume 37, Issue 3, pp 3807–3816 | Cite as

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

  • Martin Grimm
  • Oliver Feyen
  • Heiko Hofmann
  • Peter Teriete
  • Thorsten Biegner
  • Adelheid Munz
  • Siegmar Reinert
Original Article

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.

Keywords

Oral squamous cell carcinoma Immunophenotyping Immunotherapy Cytotoxic T cells Regulatory T cells 

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

Notes

Acknowledgments

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

Compliance with ethical standards

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.

Conflicts of interest

None

Consent to participate

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

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Martin Grimm
    • 1
  • Oliver Feyen
    • 2
  • Heiko Hofmann
    • 3
  • Peter Teriete
    • 4
  • Thorsten Biegner
    • 5
  • Adelheid Munz
    • 1
  • Siegmar Reinert
    • 1
  1. 1.Department of Oral and Maxillofacial SurgeryUniversity Hospital TübingenTübingenGermany
  2. 2.Zyagnum AG, Reißstraße 1aPfungstadtGermany
  3. 3.biovis’ Diagnostik MVZLimburg an der LahnGermany
  4. 4.Cancer Research CenterSanford-Burnham Medical Research InstituteLa JollaUSA
  5. 5.Department of PathologyUniversity Hospital TübingenTübingenGermany

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