title: Immunophenotyping of patients with oral squamous cell carcinoma in peripheral blood and associated tumor tissue.
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(+)/CD127(low)), 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.
authors.affiliation: Department of Oral and Maxillofacial Surgery, University Hospital Tübingen, Osianderstrasse 2-8, 72076, Tübingen, Germany. dr.dr.martingrimm@googlemail.com.
authors.forename: Martin
authors.initials: M
authors.lastname: Grimm
authors.affiliation: Zyagnum AG, Reißstraße 1a, 64319, Pfungstadt, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Feyen
authors.affiliation: biovis' Diagnostik MVZ, Justus-Staudt-Straße 2, 65555, Limburg an der Lahn, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Hofmann
authors.affiliation: Cancer Research Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Teriete
authors.affiliation: Department of Pathology, University Hospital Tübingen, Liebermeisterstrasse 8, 72076, Tübingen, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Biegner
authors.affiliation: Department of Oral and Maxillofacial Surgery, University Hospital Tübingen, Osianderstrasse 2-8, 72076, Tübingen, Germany.
authors.forename: Adelheid
authors.initials: A
authors.lastname: Munz
authors.affiliation: Department of Oral and Maxillofacial Surgery, University Hospital Tübingen, Osianderstrasse 2-8, 72076, Tübingen, Germany.
authors.forename: Siegmar
authors.initials: S
authors.lastname: Reinert
mesh_terms: D017209:Apoptosis / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000276:immunology* / Q000601:surgery; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping / Q000379:methods*; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism; D008297:Male; D009062:Mouth Neoplasms / Q000097:blood / Q000276:immunology* / Q000601:surgery; D011446:Prospective Studies; D015203:Reproducibility of Results; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism
keywords: Cytotoxic T cells; Immunophenotyping; Immunotherapy; Oral squamous cell carcinoma; Regulatory T cells