Skip to main content
Top
Published in: European Archives of Oto-Rhino-Laryngology 5/2019

01-05-2019 | Radiotherapy | Head & Neck

Treatment-induced changes of lymphocyte subsets in patients with adenoid cystic carcinoma of the head and neck

Authors: S. S. Jeske, S. E. Weissinger, J. A. Veit, C. Brunner, U. Huber, M. N. Theodoraki, T. K. Hoffmann, P. J. Schuler, Johannes Doescher

Published in: European Archives of Oto-Rhino-Laryngology | Issue 5/2019

Login to get access

Abstract

Purpose

Adenoid cystic carcinoma (ACC) of the head and neck is a rare and highly malignant tumor, characterized by perineural growth and early distant metastases. The composition of immune cells in the peripheral blood and the tumor microenvironment is critical to tumor growth and control. However, little is known about the frequency and function of the relevant immune cell subsets in this entity.

Methods

In ACC patients (n = 11) and matched healthy donors (n = 11), the frequency of peripheral blood T and B cells was measured by flow cytometry at different treatment stages of disease (24 samples). Cells were further characterized by their expression of CCR7, PD-1, CD39 and CD73. Tumor-infiltrating lymphocytes (TIL) were analyzed by immunohistochemistry for ten patients and for three patients by flow cytometry.

Results

CD4+ T cells had significantly lower frequency after radiotherapy (RT). All other cell frequencies, including Treg, were stable through course of the disease. In B cells, CD73 was reduced after RT. CCR7 expression on T and B cells in patients with relapse/metastases (R/M) differed significantly from patients with active disease. PD-1 remained stable. Treg were more present in TIL compared to peripheral blood.

Conclusion

Composition of lymphocyte subgroups behaves similar to squamous cell carcinoma in the head and neck, except for Treg, which remained stable. Nevertheless, the CD4+/Treg ratio was lower after RT, which could stand for an immunosuppressive effect in these patients. Therefore, it could be beneficial treating ACC with combined RT and immunomodulatory drugs.
Appendix
Available only for authorised users
Literature
1.
go back to reference Chae YK, Chung SY, Davis AA et al (2015) Adenoid cystic carcinoma: current therapy and potential therapeutic advances based on genomic profiling. Oncotarget 6:37117–37134CrossRefPubMedPubMedCentral Chae YK, Chung SY, Davis AA et al (2015) Adenoid cystic carcinoma: current therapy and potential therapeutic advances based on genomic profiling. Oncotarget 6:37117–37134CrossRefPubMedPubMedCentral
2.
go back to reference Lloyd S, Yu JB, Wilson LD, Decker RH (2011) Determinants and patterns of survival in adenoid cystic carcinoma of the head and neck, including an analysis of adjuvant radiation therapy. Am J Clin Oncol Cancer Clin Trials 34:76–81CrossRef Lloyd S, Yu JB, Wilson LD, Decker RH (2011) Determinants and patterns of survival in adenoid cystic carcinoma of the head and neck, including an analysis of adjuvant radiation therapy. Am J Clin Oncol Cancer Clin Trials 34:76–81CrossRef
3.
go back to reference Thompson LDR, Penner C, Ho NJ et al (2014) Sinonasal tract and nasopharyngeal adenoid cystic carcinoma: a clinicopathologic and immunophenotypic study of 86 cases. Head Neck Pathol 8:88–109CrossRefPubMed Thompson LDR, Penner C, Ho NJ et al (2014) Sinonasal tract and nasopharyngeal adenoid cystic carcinoma: a clinicopathologic and immunophenotypic study of 86 cases. Head Neck Pathol 8:88–109CrossRefPubMed
4.
go back to reference Coca-Pelaz A, Rodrigo JP, Bradley PJ et al (2015) Adenoid cystic carcinoma of the head and neck—an update. Oral Oncol 51:652–661CrossRefPubMed Coca-Pelaz A, Rodrigo JP, Bradley PJ et al (2015) Adenoid cystic carcinoma of the head and neck—an update. Oral Oncol 51:652–661CrossRefPubMed
5.
go back to reference Rettig EM, Talbot CC, Sausen M et al (2016) Whole-genome sequencing of salivary gland adenoid cystic carcinoma. Cancer Prev Res (Phila) 9:265–274 Rettig EM, Talbot CC, Sausen M et al (2016) Whole-genome sequencing of salivary gland adenoid cystic carcinoma. Cancer Prev Res (Phila) 9:265–274
6.
go back to reference Chang H, Kim JS, Choi YJ et al (2017) Overexpression of PD-L2 is associated with shorter relapse-free survival in patients with malignant salivary gland tumors. Onco Targets Ther 10:2983–2992CrossRefPubMedPubMedCentral Chang H, Kim JS, Choi YJ et al (2017) Overexpression of PD-L2 is associated with shorter relapse-free survival in patients with malignant salivary gland tumors. Onco Targets Ther 10:2983–2992CrossRefPubMedPubMedCentral
7.
go back to reference Sato E, Olson SH, Ahn J et al (2005) Intraepithelial CD8 + tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci USA 102:18538–18543CrossRefPubMedPubMedCentral Sato E, Olson SH, Ahn J et al (2005) Intraepithelial CD8 + tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci USA 102:18538–18543CrossRefPubMedPubMedCentral
8.
go back to reference Lai C, August S, Albibas A et al (2016) OX40 + regulatory T cells in cutaneous squamous cell carcinoma suppress effector T-cell responses and associate with metastatic potential. Clin Cancer Res 22:4236–4248CrossRefPubMedPubMedCentral Lai C, August S, Albibas A et al (2016) OX40 + regulatory T cells in cutaneous squamous cell carcinoma suppress effector T-cell responses and associate with metastatic potential. Clin Cancer Res 22:4236–4248CrossRefPubMedPubMedCentral
9.
go back to reference Clarke SL, Betts GJ, Plant A et al (2006) CD4 + CD25 + FOXP3 + regulatory T cells suppress anti-tumor immune responses in patients with colorectal cancer. PLoS One 1:e129CrossRefPubMedPubMedCentral Clarke SL, Betts GJ, Plant A et al (2006) CD4 + CD25 + FOXP3 + regulatory T cells suppress anti-tumor immune responses in patients with colorectal cancer. PLoS One 1:e129CrossRefPubMedPubMedCentral
10.
go back to reference Coronella JA, Telleman P, Kingsbury GA et al (2001) Evidence for an antigen-driven humoral immune response in medullary ductal breast cancer. Cancer Res 61:7889–7899PubMed Coronella JA, Telleman P, Kingsbury GA et al (2001) Evidence for an antigen-driven humoral immune response in medullary ductal breast cancer. Cancer Res 61:7889–7899PubMed
11.
go back to reference Milne K, Kobel M, Kalloger SE et al (2009) Systematic analysis of immune infiltrates in high-grade serous ovarian cancer reveals CD20, FoxP3 and TIA-1 as positive prognostic factors. PLoS One 4:e6412CrossRefPubMedPubMedCentral Milne K, Kobel M, Kalloger SE et al (2009) Systematic analysis of immune infiltrates in high-grade serous ovarian cancer reveals CD20, FoxP3 and TIA-1 as positive prognostic factors. PLoS One 4:e6412CrossRefPubMedPubMedCentral
12.
go back to reference Riemann D, Wenzel K, Schulz T et al (1997) Phenotypic analysis of T lymphocytes isolated from non-small-cell lung cancer. Int Arch Allergy Immunol 114:38–45CrossRefPubMed Riemann D, Wenzel K, Schulz T et al (1997) Phenotypic analysis of T lymphocytes isolated from non-small-cell lung cancer. Int Arch Allergy Immunol 114:38–45CrossRefPubMed
13.
go back to reference Distel LV, Fickenscher R, Dietel K et al (2009) Tumour infiltrating lymphocytes in squamous cell carcinoma of the oro- and hypopharynx: prognostic impact may depend on type of treatment and stage of disease. Oral Oncol 45:e167–e174CrossRefPubMed Distel LV, Fickenscher R, Dietel K et al (2009) Tumour infiltrating lymphocytes in squamous cell carcinoma of the oro- and hypopharynx: prognostic impact may depend on type of treatment and stage of disease. Oral Oncol 45:e167–e174CrossRefPubMed
14.
go back to reference Czystowska M, Gooding W, Szczepanski MJ et al (2013) The immune signature of CD8(+)CCR7(+) T cells in the peripheral circulation associates with disease recurrence in patients with HNSCC. Clin Cancer Res 19:889–899CrossRefPubMed Czystowska M, Gooding W, Szczepanski MJ et al (2013) The immune signature of CD8(+)CCR7(+) T cells in the peripheral circulation associates with disease recurrence in patients with HNSCC. Clin Cancer Res 19:889–899CrossRefPubMed
15.
go back to reference Li J, Jie H-B, Lei Y et al (2015) PD-1/SHP-2 inhibits Tc1/Th1 phenotypic responses and the activation of T cells in the tumor microenvironment. Cancer Res 75:508–518CrossRefPubMed Li J, Jie H-B, Lei Y et al (2015) PD-1/SHP-2 inhibits Tc1/Th1 phenotypic responses and the activation of T cells in the tumor microenvironment. Cancer Res 75:508–518CrossRefPubMed
16.
go back to reference Lechner A, Schlößer H, Rothschild SI et al (2017) Characterization of tumor-associated T-lymphocyte subsets and immune checkpoint molecules in head and neck squamous cell carcinoma. Oncotarget 8:44418–44433CrossRefPubMedPubMedCentral Lechner A, Schlößer H, Rothschild SI et al (2017) Characterization of tumor-associated T-lymphocyte subsets and immune checkpoint molecules in head and neck squamous cell carcinoma. Oncotarget 8:44418–44433CrossRefPubMedPubMedCentral
17.
go back to reference Ferris RL, Blumenschein G Jr, Fayette J et al (2016) Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med 375:1856–1867CrossRefPubMedPubMedCentral Ferris RL, Blumenschein G Jr, Fayette J et al (2016) Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med 375:1856–1867CrossRefPubMedPubMedCentral
18.
19.
go back to reference Blay J, White TD, Hoskin DW (1997) The extracellular fluid of solid carcinomas contains immunosuppressive concentrations of adenosine. Cancer Res 57:2602–2605PubMed Blay J, White TD, Hoskin DW (1997) The extracellular fluid of solid carcinomas contains immunosuppressive concentrations of adenosine. Cancer Res 57:2602–2605PubMed
20.
21.
go back to reference Schuler PJ, Schilling B, Harasymczuk M et al (2012) Phenotypic and functional characteristics of CD4 + CD39 + FOXP3 + and CD4 + CD39 + FOXP3neg T-cell subsets in cancer patients. Eur J Immunol 42:1876–1885CrossRefPubMedPubMedCentral Schuler PJ, Schilling B, Harasymczuk M et al (2012) Phenotypic and functional characteristics of CD4 + CD39 + FOXP3 + and CD4 + CD39 + FOXP3neg T-cell subsets in cancer patients. Eur J Immunol 42:1876–1885CrossRefPubMedPubMedCentral
22.
go back to reference Schuler PJ, Harasymczuk M, Schilling B et al (2011) Separation of human CD4 + CD39 + T cells by magnetic beads reveals two phenotypically and functionally different subsets. J Immunol Methods 369:59–68CrossRefPubMedPubMedCentral Schuler PJ, Harasymczuk M, Schilling B et al (2011) Separation of human CD4 + CD39 + T cells by magnetic beads reveals two phenotypically and functionally different subsets. J Immunol Methods 369:59–68CrossRefPubMedPubMedCentral
23.
go back to reference Schuler PJ, Macatangay BJ, Saze Z et al (2013) CD4(+)CD73(+) T cells are associated with lower T-cell activation and C reactive protein levels and are depleted in HIV-1 infection regardless of viral suppression. Aids 27:1545–1555CrossRefPubMed Schuler PJ, Macatangay BJ, Saze Z et al (2013) CD4(+)CD73(+) T cells are associated with lower T-cell activation and C reactive protein levels and are depleted in HIV-1 infection regardless of viral suppression. Aids 27:1545–1555CrossRefPubMed
24.
go back to reference Ziebart A, Huber U, Jeske S et al (2018) The influence of chemotherapy on adenosine-producing B cells in patients with head and neck squamous cell carcinoma. Oncotarget 9:5834–5847CrossRefPubMed Ziebart A, Huber U, Jeske S et al (2018) The influence of chemotherapy on adenosine-producing B cells in patients with head and neck squamous cell carcinoma. Oncotarget 9:5834–5847CrossRefPubMed
25.
go back to reference Moncrieffe H, Nistala K, Kamhieh Y et al (2010) High expression of the ectonucleotidase CD39 on T cells from the inflamed site identifies two distinct populations, one regulatory and one memory T cell population. J Immunol 185:134–143CrossRefPubMed Moncrieffe H, Nistala K, Kamhieh Y et al (2010) High expression of the ectonucleotidase CD39 on T cells from the inflamed site identifies two distinct populations, one regulatory and one memory T cell population. J Immunol 185:134–143CrossRefPubMed
26.
go back to reference Wagner D-C, Roth W (2018) Prognostic significance of immune cell infiltrates in tumor pathology. Pathologe 39:532–538CrossRefPubMed Wagner D-C, Roth W (2018) Prognostic significance of immune cell infiltrates in tumor pathology. Pathologe 39:532–538CrossRefPubMed
27.
go back to reference Sridharan V, Gjini E, Liao X et al (2016) Immune profiling of adenoid cystic carcinoma: PD-L2 expression and associations with tumor-infiltrating lymphocytes. Cancer Immunol Res 4:679–687CrossRefPubMed Sridharan V, Gjini E, Liao X et al (2016) Immune profiling of adenoid cystic carcinoma: PD-L2 expression and associations with tumor-infiltrating lymphocytes. Cancer Immunol Res 4:679–687CrossRefPubMed
28.
go back to reference Schuler PJ, Harasymczuk M, Schilling B et al (2013) Effects of adjuvant chemoradiotherapy on the frequency and function of regulatory T cells in patients with head and neck cancer. Clin Cancer Res 19:6585–6596CrossRefPubMed Schuler PJ, Harasymczuk M, Schilling B et al (2013) Effects of adjuvant chemoradiotherapy on the frequency and function of regulatory T cells in patients with head and neck cancer. Clin Cancer Res 19:6585–6596CrossRefPubMed
29.
go back to reference Ebert LM, Schaerli P, Moser B (2005) Chemokine-mediated control of T cell traffic in lymphoid and peripheral tissues. Mol Immunol 42:799–809CrossRefPubMed Ebert LM, Schaerli P, Moser B (2005) Chemokine-mediated control of T cell traffic in lymphoid and peripheral tissues. Mol Immunol 42:799–809CrossRefPubMed
30.
go back to reference Hanke T, Melling N, Simon R et al (2015) High intratumoral FOXP3(+) T regulatory cell (Tregs) density is an independent good prognosticator in nodal negative colorectal cancer. Int J Clin Exp Pathol 8:8227–8235PubMedPubMedCentral Hanke T, Melling N, Simon R et al (2015) High intratumoral FOXP3(+) T regulatory cell (Tregs) density is an independent good prognosticator in nodal negative colorectal cancer. Int J Clin Exp Pathol 8:8227–8235PubMedPubMedCentral
31.
go back to reference Spranger S (2016) Mechanisms of tumor escape in the context of the T-cell-inflamed and the non-T-cell-inflamed tumor microenvironment. Int Immunol 28:383–391CrossRefPubMedPubMedCentral Spranger S (2016) Mechanisms of tumor escape in the context of the T-cell-inflamed and the non-T-cell-inflamed tumor microenvironment. Int Immunol 28:383–391CrossRefPubMedPubMedCentral
Metadata
Title
Treatment-induced changes of lymphocyte subsets in patients with adenoid cystic carcinoma of the head and neck
Authors
S. S. Jeske
S. E. Weissinger
J. A. Veit
C. Brunner
U. Huber
M. N. Theodoraki
T. K. Hoffmann
P. J. Schuler
Johannes Doescher
Publication date
01-05-2019
Publisher
Springer Berlin Heidelberg
Keyword
Radiotherapy
Published in
European Archives of Oto-Rhino-Laryngology / Issue 5/2019
Print ISSN: 0937-4477
Electronic ISSN: 1434-4726
DOI
https://doi.org/10.1007/s00405-019-05363-2

Other articles of this Issue 5/2019

European Archives of Oto-Rhino-Laryngology 5/2019 Go to the issue