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

被引:28
作者
Grimm, Martin [1 ]
Feyen, Oliver [2 ]
Hofmann, Heiko [3 ]
Teriete, Peter [4 ]
Biegner, Thorsten [5 ]
Munz, Adelheid [1 ]
Reinert, Siegmar [1 ]
机构
[1] Univ Tubingen Hosp, Dept Oral & Maxillofacial Surg, Osianderstr 2-8, D-72076 Tubingen, Germany
[2] Zyagnum AG, Reisstr 1a, D-64319 Pfungstadt, Germany
[3] Biovis Diagnost MVZ, Justus Staudt Str 2, D-65555 Limburg An Der Lahn, Germany
[4] Sanford Burnham Med Res Inst, Canc Res Ctr, 10901 N Torrey Pines Rd, La Jolla, CA 92037 USA
[5] Univ Tubingen Hosp, Dept Pathol, Liebermeisterstr 8, D-72076 Tubingen, Germany
关键词
Oral squamous cell carcinoma; Immunophenotyping; Immunotherapy; Cytotoxic T cells; Regulatory T cells; MEDIATED IMMUNE-RESPONSES; REGULATORY T-CELLS; INFILTRATING LYMPHOCYTES; NECK-CANCER; INCREASED FREQUENCY; INDUCE APOPTOSIS; FAS LIGAND; HEAD; SUBPOPULATIONS; MICROENVIRONMENT;
D O I
10.1007/s13277-015-4224-2
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:3807 / 3816
页数:10
相关论文
共 41 条
[31]   The Tubingen approach: identification, selection, and validation of tumor-associated HLA peptides for cancer therapy [J].
Singh-Jasuja, H ;
Emmerich, NPN ;
Rammensee, HG .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 2004, 53 (03) :187-195
[32]   Th2 subset dominance among peripheral blood T lymphocytes in patients with digestive cancers [J].
Tabata, T ;
Hazama, S ;
Yoshino, S ;
Oka, M .
AMERICAN JOURNAL OF SURGERY, 1999, 177 (03) :203-208
[33]  
Tanaka H, 1999, J IMMUNOL, V162, P3574
[34]   Neoadjuvant immunotherapy of oral squamous cell carcinoma modulates intratumoral CD4/CD8 ratio and tumor microenvironment:: A multicenter phase II clinical trial [J].
Tímár, J ;
Ladányi, A ;
Forster-Horváth, C ;
Lukits, J ;
Döme, B ;
Remenár, P ;
Gödény, M ;
Kásler, M ;
Bencsik, B ;
Répássy, G ;
Szabó, G ;
Velich, N ;
Suba, Z ;
Élö, J ;
Balatoni, Z ;
Pócza, K ;
Zemplén, B ;
Chretien, P ;
Talor, E .
JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (15) :3421-3432
[35]   Tumor infiltrating lymphocytes (TIL) and prognosis in oral cavity squamous carcinoma: A preliminary study [J].
Wolf, Gregory T. ;
Chepeha, Douglas B. ;
Bellile, Emily ;
Nguyen, Ariane ;
Thomas, Daffyd ;
McHugh, Jonathan .
ORAL ONCOLOGY, 2015, 51 (01) :90-95
[36]  
WOLF GT, 1987, ARCH OTOLARYNGOL, V113, P1200
[37]   LYMPHOCYTE SUBPOPULATIONS INFILTRATING SQUAMOUS CARCINOMAS OF THE HEAD AND NECK - CORRELATIONS WITH EXTENT OF TUMOR AND PROGNOSIS [J].
WOLF, GT ;
HUDSON, JL ;
PETERSON, KA ;
MILLER, HL ;
MCCLATCHEY, KD .
OTOLARYNGOLOGY-HEAD AND NECK SURGERY, 1986, 95 (02) :142-152
[38]   Differences in oral habit and lymphocyte subpopulation affect malignant transformation of patients with oral precancer [J].
Yeh, Chien-Yang ;
Lin, Chien-Ling ;
Chang, Mei-Chi ;
Chen, Hsin-Ming ;
Kok, Seng-Heng ;
Chang, Shu-Hui ;
Kuo, Ying-Shiung ;
Hahn, Liang-Jiunn ;
Chan, Chiu-Po ;
Lee, Jang-Jaer ;
Jeng, Jiiang-Huei .
JOURNAL OF THE FORMOSAN MEDICAL ASSOCIATION, 2016, 115 (04) :263-268
[39]   Immune checkpoint modulation: Rational design of combination strategies [J].
Zamarin, Dmitriy ;
Postow, Michael A. .
PHARMACOLOGY & THERAPEUTICS, 2015, 150 :23-32
[40]   FOXP3: Of mice and men [J].
Ziegler, Steven F. .
ANNUAL REVIEW OF IMMUNOLOGY, 2006, 24 :209-226