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Pathology & Oncology Research
Published in: Pathology & Oncology Research 3/2018

Open Access 01-07-2018 | Original Article

Immunohistochemical Analysis of Foxp3+, CD4+, CD8+ Cell Infiltrates and PD-L1 in Oral Squamous Cell Carcinoma

Authors: Olga Stasikowska-Kanicka, Małgorzata Wągrowska-Danilewicz, Marian Danilewicz

Published in: Pathology & Oncology Research | Issue 3/2018

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Abstract

The immunoexpression of the PD-L1 and the number of immune infiltrating cells have been shown to be a significant prognostic factors in various human cancers. Immunohistochemical method was used to examine the immunoexpression of PD-L1 and number of Foxp3+, CD4+, CD8+ cells in 78 cases of oral squamous cell carcinomas (OSCCs): with better prognosis - OSCCBP (n = 37), and with poorer prognosis - OSCCPP (n = 41), and 18 cases of normal mucosa as a control. The immunoexpression of PD-L1 and the mean number of Foxp3+ cells was significantly increased in OSCCPP group in comparison to OSCCBP and control groups. The mean number of CD4+ cells was significantly increased in OSCCPP group in comparison to OSCCBP and control groups. CD8+ cells were significantly more numerous in OSCCBP group in comparison to OSCCPP and control group. In both OSCCPP and OSCCBP groups there were positive significant correlations between number of Foxp3+ and CD4+ cells. We found positive correlations between the immunoexpression of PD-L1 and numbers of Foxp3+ cells, and negative correlation between the immunoexpression of PD-L1 and numbers of CD8+ cells in both OSCCPP and OSCCBP groups. We found also significant positive correlation between immunoexpression of PD-L1 and the number of CD4+ cells in OSCCPP group. In conclusion, our findings support the hypothesis of involvement of Tregs and PD-L1 in OSCC development and progression.
Literature
1.
2.
Byakodi R, Byakodi S, Hiremath S et al (2012) Oral cancer in India: an epidemiologic and clinical review. J Community Health 37:316–319CrossRefPubMed
3.
4.
5.
Wang RF (2008) CD8+ regulatory T cells, their suppressive mechanisms, and regulation in cancer. Hum Immunol 69:811–814CrossRefPubMed
6.
Zhang S, Ke X, Zeng S, et al (2015) Analysis of CD8+ Treg cells in patients with ovarian cancer: a possible mechanism for immune impairment. Cell Mol Immunol Sep;12(5):580–591
7.
Chaudhry A, Rudra D, Treuting P et al (2009) CD4 regulatory T cells control TH17 responses in a Stat3-dependent manner. Science 326(5955):98691CrossRef
8.
9.
Sakaguchi S, Miyara M, Costantino CM et al (2010) FOXP3+ regulatory T cells in the human immune system. Nat Rev Immunol 10:490–500CrossRefPubMed
10.
Hori S, Nomura T, Sakaguchi S (2003) Control of regulatory T cell development by the transcription factor Foxp3. Science 299:1057–1061CrossRefPubMed
11.
Von Boehmer H (2005) Mechanisms of suppression by suppressor T cells. Nat Immunol 6(4):338–344CrossRef
12.
DiPaolo RJ, Glass DD, Bijwaard KE et al (2005) CD4+CD25+ T cells prevent the development of organ-specific autoimmune disease by inhibiting the differentiation of autoreactive effector T cells. J Immunol 175:7135–7142CrossRefPubMed
13.
Sakaguchi S (2005) Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat Immunol 6:345–352CrossRefPubMed
14.
Oleinika K, Nibbs RJ, Graham GJ et al (2013) Suppression, subversion and escape: the role of regulatory T cells in cancer progression. Clin Exp Immunol 171:36–45CrossRefPubMed
15.
Chen L (2004) Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity. Nat Rev Immunol 4(5):336–347CrossRefPubMed
16.
Park JJ, Omiya R, Matsumura Y et al (2010) B7–H1/CD80 interaction is required for the induction and maintenance of peripheral T-cell tolerance. Blood 116(8):1291–1298CrossRefPubMedPubMedCentral
17.
Sharpe AH, Wherry EJ, Ahmed R et al (2007) The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection. Nat Immunol 8:239–245CrossRefPubMed
18.
Freeman GJ, Long AJ, Iwai Y et al (2000) Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 192:1027–1034CrossRefPubMedPubMedCentral
19.
Hino R, Kabashima K, Kato Y et al (2010) Tumor cell expression of programmed cell death-1 ligand 1 is a prognostic factor for malignant melanoma. Cancer 116(7):1757–1766CrossRefPubMed
20.
Shi SJ, Wang LJ, Wang GD et al (2013) B7-H1 expression is associated with poor prognosis in colorectal carcinoma and regulates the proliferation and invasion of HCT116 colorectal cancer cells. PLoS One 8(10):e76012CrossRefPubMedPubMedCentral
21.
Velcheti V, Schalper KA, Carvajal DE et al (2014) Programmed death ligand-1 expression in non-small cell lung cancer. Lab Investig 94(1):107–116CrossRefPubMed
22.
Chen XL, Yuan SX, Chen C et al (2009) Expression of B7-H1 protein in human pancreatic carcinoma tissues and its clinical significance. Chin J Cancer 28(12):1328–1332CrossRef
23.
Gao Q, Wang XY, Qiu SJ et al (2009) Overexpression of PD-L1 significantly associates with tumor aggressiveness and postoperative recurrence in human hepatocellular carcinoma. Clin Cancer Res 15(3):971–979CrossRefPubMed
24.
25.
26.
Barnes L, Everson JW, Reichart P, et al (2005) World Health Organization classification of Tumours. Pathology and Genetics Head and Neck Tumours IARC Press Lyon 168–176
27.
Drennan S, Stafford ND, Greenman J et al (2013) Increased frequency and suppressive activity of CD127 Treg cells in the peripheral circulation of patients with head and neck squamous cell carcinoma are associated with advanced stage and nodal involvement. Immunology. doi:10.​1111/​imm.​12144
28.
Schott AK, Pries R, Wollenberg B (2010) Permanent up-regulation of regulatory T-lymphocytes in patients with head and neck cancer. Int J Mol Med 26:67–75PubMed
29.
Liang YJ, Liu HC, Su YX et al (2011) Foxp3 expressed by tongue squamous cell carcinoma cells correlates with clinicopathologic features and overall survival in tongue squamous cell carcinoma patients. Oral Oncol 47(7):566–570CrossRefPubMed
30.
Hinz S, Pagerols-Raluy L, Oberg HH et al (2007) Foxp3 expression in pancreatic carcinoma cells as a novel mechanism of immune evasion in cancer. Cancer Res 67(17):8344–8350CrossRefPubMed
31.
Merlo A, Casalini P, Carcangiu ML et al (2009) FOXP3 expression and overall survival in breast cancer. J Clin Oncol 27(11):1746–1752CrossRefPubMed
32.
Chen CX, Rowell WA, Thomas RM et al (2006) Transcriptional regulation by Foxp3 is associated with direct promoter occupancy and modulation of histone acetylation. J Biol Chem 281:36828–36834CrossRefPubMed
33.
Hiraoka N, Onozato K, Kosuge T et al (2006) Prevalence of FOXP3+ regulatory T cells increases during the progression of pancreatic ductal adenocarcinoma and its premalignant lesions. Clin Cancer Res 12:5423–5434CrossRefPubMed
34.
Kobayashi N, Hiraoka N, Yamagami W et al (2007) FOXP3+ regulatory T cells affect the development and progression of hepatocarcinogenesis. Clin Cancer Res 13:902–911CrossRefPubMed
35.
Bohling SD, Allison KH (2008) Immunosuppressive regulatory T cells are associated with aggressive breast cancer phenotypes: a potential therapeutic target. Mod Pathol 21:1527–1532CrossRefPubMed
36.
Suzuki H, Chikazawa N, Tasaka T et al (2010) Intratumoral CD8(+) T/FOXP3 (+) cell ratio is a predictive marker for survival in patients with colorectal cancer. Cancer Immunol Immunother 59(5):653–661CrossRefPubMed
37.
Ma MW, Medicherla RC, Qian M et al (2012) Immune response in melanoma: an in-depth analysis of the primary tumor and corresponding sentinel lymph node. Mod Pathol 25:1000–1010CrossRefPubMed
38.
Kim M, Grimmig T, Grimm M et al (2013) Expression of Foxp3 in colorectal cancer but not in Treg cells correlates with disease progression in patients with colorectal cancer. PLoS One 8(1):e53630CrossRefPubMedPubMedCentral
39.
Salama P, Phillips M, Grieu F et al (2009) Tumor-infiltrating FOXP3+ T regulatory cells show strong prognostic significance in colorectal cancer. J Clin Oncol 27(2):186–192CrossRefPubMed
40.
Correale P, Rotundo MS, Del Vecchio MT et al (2010) Regulatory (FoxP3+) T-cell tumor infiltration is a favorable prognostic factor in advanced colon cancer patients undergoing chemo or chemoimmunotherapy. J Immunother 33:435–441CrossRefPubMed
41.
Viglietta V, Baecher-Allan C, Weiner HL et al (2004) Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis. J Exp Med 199:971–979CrossRefPubMedPubMedCentral
42.
Watanabe MAE, Oda JMM, Amarante MK et al (2010) Regulatory T cells and breast cancer: implications for immunopathogenesis. Cancer Metastasis Rev 29:569–579CrossRefPubMed
43.
Knutson KL, Dang Y, Lu H et al (2006) IL-2 immunotoxin therapy modulates tumor-associated regulatory T cells and leads to lasting immune-mediated rejection of breast cancers in neu-transgenic mice. J Immunol 177:84–91CrossRefPubMed
44.
Zhu S, Lin J, Qiao G et al (2015) Differential regulation and function of tumor-infiltrating T cells in different stages of breast cancer patients. Tumour Biol 36(10):7907–7913CrossRefPubMed
45.
46.
Dhodapkar MV, Sznol M, Zhao B et al (2014) Induction of antigen-specific immunity with a vaccine targeting NY-ESO-1 to the dendritic cell receptor DEC-205. Sci Transl Med 6:232–251CrossRef
47.
Miyara M, Sakaguchi S (2011) Human FoxP3(+)CD4(+) regulatory T cells: their knowns and unknowns. Immunol Cell Biol 89(3):346–351CrossRefPubMed
48.
Ohigashi Y, Sho M, Yamada Y et al (2005) Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand-2 expression in human esophageal cancer. Clin Cancer Res 11:2947–2953CrossRefPubMed
49.
Lyford-Pike S, Peng S, Young GD, et al (2013) Evidence for a role of the PD-1:PD-L1 pathway in immune resistance of HPV-associated head and neck squamous cell carcinoma. Cancer Res 15;73(6):1733-1741
50.
Hirano F, Kaneko K, Tamura H et al (2005) Blockade of B7–H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity. Cancer Res 65(3):1089–1096PubMed
51.
Thompson ED, Zahurak M, Murphy A et al (2016) Patterns of PD-L1 expression and CD8 T cell infiltration in gastric adenocarcinomas and associated immune stroma. Gut. doi:10.​1136/​gutjnl-2015-310839
52.
53.
Tokito T, Azuma K, Kawahara A et al (2016) Predictive relevance of PD-L1 expression combined with CD8+ TIL density in stage III non-small cell lung cancer patients receiving concurrent chemoradiotherapy. Eur J Cancer 55:7–14CrossRefPubMed
Metadata
Title
Immunohistochemical Analysis of Foxp3+, CD4+, CD8+ Cell Infiltrates and PD-L1 in Oral Squamous Cell Carcinoma
Authors
Olga Stasikowska-Kanicka
Małgorzata Wągrowska-Danilewicz
Marian Danilewicz
Publication date
01-07-2018
Publisher
Springer Netherlands
Published in
Pathology & Oncology Research / Issue 3/2018
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI
https://doi.org/10.1007/s12253-017-0270-y

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