Adenoid cystic carcinoma of the salivary glands: a pilot study of potential therapeutic targets and characterization of the immunological tumor environment and angiogenesis.
Adenoid cystic carcinoma
Macrophage polarization
Neovascularization
Salivary gland cancer
Journal
European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery
ISSN: 1434-4726
Titre abrégé: Eur Arch Otorhinolaryngol
Pays: Germany
ID NLM: 9002937
Informations de publication
Date de publication:
Jun 2023
Jun 2023
Historique:
received:
31
07
2022
accepted:
14
02
2023
medline:
15
5
2023
pubmed:
2
3
2023
entrez:
1
3
2023
Statut:
ppublish
Résumé
Adenoid cystic carcinoma (ACC) is a rare type of cancer commonly occurring in salivary glands. It is characterized by slow but infiltrative growth, nerve infiltration and overall poor prognosis, with late recurrence and distant metastasis. The treatment of ACC is still limited to surgery and/or (adjuvant) radiotherapy. Till now no promising systemic therapy option exists. However, various studies deliver promising results after treatment with anti-angiogenetic agents, such as anti-EGFR-antibody Cetuximab or Tyrosinkinase inhibitor Lenvatinib. By using of immunohistological methods we analyzed and compared the macrophage and lymphocyte populations, vascularization, and PD-L1-status in 12 ACC of the salivary glands. All cases showed a significant elevation of macrophages with M2 polarization and a higher vascularization in ACC compared to normal salivary gland tissue. The CD4/CD8 quotient was heterogenous. ACC does not show relevant PD-L1 expression. The predominant M2 polarization of macrophages in ACC could be responsible for elevated vascularization, as already been proved in other cancer types, that M2 macrophages promote angiogenesis.
Sections du résumé
BACKGROUND
BACKGROUND
Adenoid cystic carcinoma (ACC) is a rare type of cancer commonly occurring in salivary glands. It is characterized by slow but infiltrative growth, nerve infiltration and overall poor prognosis, with late recurrence and distant metastasis. The treatment of ACC is still limited to surgery and/or (adjuvant) radiotherapy. Till now no promising systemic therapy option exists. However, various studies deliver promising results after treatment with anti-angiogenetic agents, such as anti-EGFR-antibody Cetuximab or Tyrosinkinase inhibitor Lenvatinib.
METHODS
METHODS
By using of immunohistological methods we analyzed and compared the macrophage and lymphocyte populations, vascularization, and PD-L1-status in 12 ACC of the salivary glands.
RESULTS
RESULTS
All cases showed a significant elevation of macrophages with M2 polarization and a higher vascularization in ACC compared to normal salivary gland tissue. The CD4/CD8 quotient was heterogenous. ACC does not show relevant PD-L1 expression.
CONCLUSIONS
CONCLUSIONS
The predominant M2 polarization of macrophages in ACC could be responsible for elevated vascularization, as already been proved in other cancer types, that M2 macrophages promote angiogenesis.
Identifiants
pubmed: 36856809
doi: 10.1007/s00405-023-07884-3
pii: 10.1007/s00405-023-07884-3
pmc: PMC10175421
doi:
Substances chimiques
B7-H1 Antigen
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2937-2944Informations de copyright
© 2023. The Author(s).
Références
Hellquist H, Skalova A (2014) Adenoid cystic carcinoma. Springer, Berlin, pp 221–260
Du F, Zhou CX, Gao Y (2016) Myoepithelial differentiation in cribriform, tubular and solid pattern of adenoid cystic carcinoma: a potential involvement in histological grading and prognosis. Ann Diagn Pathol 22:12–17. https://doi.org/10.1016/j.anndiagpath.2016.03.001
doi: 10.1016/j.anndiagpath.2016.03.001
pubmed: 27180054
Liu X, Yang X, Zhan C, Zhang Y, Hou J, Yin X (2020) Perineural invasion in adenoid cystic carcinoma of the salivary glands: where we are and where we need to go. Front Oncol 10:1493. https://doi.org/10.3389/fonc.2020.01493
doi: 10.3389/fonc.2020.01493
pubmed: 33014792
pmcid: 7461905
Bell D, Roberts D, Kies M, Rao P, Weber RS, El-Naggar AK (2010) Cell type-dependent biomarker expression in adenoid cystic carcinoma. Cancer 116(24):5749–5756. https://doi.org/10.1002/cncr.25541
doi: 10.1002/cncr.25541
pubmed: 20824717
Nightingale J, Lum B, Ladwa R, Simpson F, Panizza B (2021) Adenoid cystic carcinoma: a review of clinical features, treatment targets and advances in improving the immune response to monoclonal antibody therapy. Biochim Biophys Acta Rev Cancer 1875(2):188523. https://doi.org/10.1016/j.bbcan.2021.188523
doi: 10.1016/j.bbcan.2021.188523
pubmed: 33600823
Mosconi C, de Arruda JAA, de Farias ACR, Oliveira GAQ, de Paula HM, Fonseca FP et al (2019) Immune microenvironment and evasion mechanisms in adenoid cystic carcinomas of salivary glands. Oral Oncol 88:95–101. https://doi.org/10.1016/j.oraloncology.2018.11.028
doi: 10.1016/j.oraloncology.2018.11.028
pubmed: 30616805
Afonina IS, Cullen SP, Martin SJ (2010) Cytotoxic and non-cytotoxic roles of the CTL/NK protease granzyme B. Immunol Rev 235(1):105–116. https://doi.org/10.1111/j.0105-2896.2010.00908.x
doi: 10.1111/j.0105-2896.2010.00908.x
pubmed: 20536558
Wang J, Li R, Cao Y, Gu Y, Fang H, Fei Y et al (2021) Intratumoral CXCR5+CD8+T associates with favorable clinical outcomes and immunogenic contexture in gastric cancer. Nat Commun. https://doi.org/10.1038/s41467-021-23356-w
doi: 10.1038/s41467-021-23356-w
pubmed: 34934057
pmcid: 9632329
Oshi M, Asaoka M, Tokumaru Y, Yan L, Matsuyama R, Ishikawa T et al (2020) CD8 T cell score as a prognostic biomarker for triple negative breast cancer. Int J Mol Sci 21(18):6968. https://doi.org/10.3390/ijms21186968
doi: 10.3390/ijms21186968
pubmed: 32971948
pmcid: 7555570
Wang K, Shen T, Siegal GP, Wei S (2017) The CD4/CD8 ratio of tumor-infiltrating lymphocytes at the tumor-host interface has prognostic value in triple-negative breast cancer. Hum Pathol 69:110–117. https://doi.org/10.1016/j.humpath.2017.09.012
doi: 10.1016/j.humpath.2017.09.012
pubmed: 28993275
Shindo G, Endo T, Onda M, Goto S, Miyamoto Y, Kaneko T (2013) Is the CD4/CD8 ratio an effective indicator for clinical estimation of adoptive immunotherapy for cancer treatment? J Cancer Ther 04(08):1382–1390. https://doi.org/10.4236/jct.2013.48164
doi: 10.4236/jct.2013.48164
Zuazo-Gaztelu I, Casanovas O (2018) Unraveling the role of angiogenesis in cancer ecosystems. Front Oncol 8:248. https://doi.org/10.3389/fonc.2018.00248
doi: 10.3389/fonc.2018.00248
pubmed: 30013950
pmcid: 6036108
House SL, Castro AM, Lupu TS, Weinheimer C, Smith C, Kovacs A et al (2016) Endothelial fibroblast growth factor receptor signaling is required for vascular remodeling following cardiac ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol 310(5):H559–H571. https://doi.org/10.1152/ajpheart.00758.2015
doi: 10.1152/ajpheart.00758.2015
pubmed: 26747503
pmcid: 4796602
Myoken Y, Myoken Y, Okamoto T, Sato JD, Kan M, Mckeehan WL et al (1996) Immunohistochemical study of overexpression of fibroblast growth factor-1 (fgf-1), fgf-2, and fgf receptor-1 in human malignant salivary gland tumours. J Pathol 178(4):429–436. https://doi.org/10.1002/(SICI)1096-9896(199604)178:4%3c429::AID-PATH495%3e3.0.CO;2-1
doi: 10.1002/(SICI)1096-9896(199604)178:4<429::AID-PATH495>3.0.CO;2-1
pubmed: 8691322
KoochekDezfuli M, Seyedmajidi M, Nafarzadeh S, Yazdani F, Bijani A (2019) Angiogenesis and lymphangiogenesis in salivary gland adenoid cystic carcinoma and mucoepidermoid carcinoma. Asian Pacific J Cancer Prev. 20(12):3547–3553. https://doi.org/10.31557/apjcp.2019.20.12.3547
doi: 10.31557/apjcp.2019.20.12.3547
Stout RD, Jiang C, Matta B, Tietzel I, Watkins SK, Suttles J (2005) Macrophages sequentially change their functional phenotype in response to changes in microenvironmental influences. J Immunol 175(1):342–349. https://doi.org/10.4049/jimmunol.175.1.342
doi: 10.4049/jimmunol.175.1.342
pubmed: 15972667
Stout RD, Suttles J (2004) Functional plasticity of macrophages: reversible adaptation to changing microenvironments. J Leukoc Biol 76(3):509–513. https://doi.org/10.1189/jlb.0504272
doi: 10.1189/jlb.0504272
pubmed: 15218057
Mosser DM, Edwards JP (2008) Exploring the full spectrum of macrophage activation. Nat Rev Immunol 8(12):958–969. https://doi.org/10.1038/nri2448
doi: 10.1038/nri2448
pubmed: 19029990
pmcid: 2724991
Yang Y, Guo Z, Chen W, Wang X, Cao M, Han X et al (2021) M2 macrophage-derived exosomes promote angiogenesis and growth of pancreatic ductal adenocarcinoma by targeting E2F2. Mol Ther 29(3):1226–1238. https://doi.org/10.1016/j.ymthe.2020.11.024
doi: 10.1016/j.ymthe.2020.11.024
pubmed: 33221435
Yang Z, Li H, Wang W, Zhang J, Jia S, Wang J et al (2019) CCL2/CCR2 axis promotes the progression of salivary adenoid cystic carcinoma via recruiting and reprogramming the tumor-associated macrophages. Front Oncol 9:231. https://doi.org/10.3389/fonc.2019.00231
doi: 10.3389/fonc.2019.00231
pubmed: 31024838
pmcid: 6465613
Linxweiler M, Kuo F, Katabi N, Lee M, Nadeem Z, Dalin MG et al (2020) The immune microenvironment and neoantigen landscape of aggressive salivary gland carcinomas differ by subtype. Clin Cancer Res 26(12):2859–2870. https://doi.org/10.1158/1078-0432.ccr-19-3758
doi: 10.1158/1078-0432.ccr-19-3758
pubmed: 32060100
pmcid: 7918996
Rodriguez-Russo CA, Junn JC, Yom SS, Bakst RL (2021) Radiation therapy for adenoid cystic carcinoma of the head and neck. Cancers 13(24):6335. https://doi.org/10.3390/cancers13246335
doi: 10.3390/cancers13246335
pubmed: 34944955
pmcid: 8699151
Mahmood U, Bang A, Chen YH, Mak RH, Lorch JH, Hanna GJ et al (2021) A randomized phase 2 study of pembrolizumab with or without radiation in patients with recurrent or metastatic adenoid cystic carcinoma. Int J Radiat Oncol Biol Phys 109(1):134–144. https://doi.org/10.1016/j.ijrobp.2020.08.018
doi: 10.1016/j.ijrobp.2020.08.018
pubmed: 32781104
Papaspyrou G, Hoch S, Rinaldo A, Rodrigo JP, Takes RP, van Herpen C et al (2011) Chemotherapy and targeted therapy in adenoid cystic carcinoma of the head and neck: a review. Head Neck 33(6):905–911. https://doi.org/10.1002/hed.21458
doi: 10.1002/hed.21458
pubmed: 20652885
Laurie SA, Ho AL, Fury MG, Sherman E, Pfister DG (2011) Systemic therapy in the management of metastatic or locally recurrent adenoid cystic carcinoma of the salivary glands: a systematic review. Lancet Oncol 12(8):815–824. https://doi.org/10.1016/s1470-2045(10)70245-x
doi: 10.1016/s1470-2045(10)70245-x
pubmed: 21147032
Schildhaus HU (2018) Der prädiktive Wert der PD-L1-Diagnostik. Pathologe 39(6):498–519. https://doi.org/10.1007/s00292-018-0507-x
doi: 10.1007/s00292-018-0507-x
pubmed: 30367225
Rhee I (2016) Diverse macrophages polarization in tumor microenvironment. Arch Pharmacal Res 39(11):1588–1596. https://doi.org/10.1007/s12272-016-0820-y
doi: 10.1007/s12272-016-0820-y
Pan Y, Yu Y, Wang X, Zhang T (2020) Tumor-associated macrophages in tumor immunity. Front Immunol 11:583084. https://doi.org/10.3389/fimmu.2020.583084
doi: 10.3389/fimmu.2020.583084
pubmed: 33365025
pmcid: 7751482
Suarez-Lopez L, Sriram G, Kong YW, Morandell S, Merrick KA, Hernandez Y et al (2018) MK2 contributes to tumor progression by promoting M2 macrophage polarization and tumor angiogenesis. Proc Natl Acad Sci U S A 115(18):E4236–E4244. https://doi.org/10.1073/pnas.1722020115
doi: 10.1073/pnas.1722020115
pubmed: 29666270
pmcid: 5939099
Jetten N, Verbruggen S, Gijbels MJ, Post MJ, De Winther MPJ, Donners MMPC (2014) Anti-inflammatory M2, but not pro-inflammatory M1 macrophages promote angiogenesis in vivo. Angiogenesis 17(1):109–118. https://doi.org/10.1007/s10456-013-9381-6
doi: 10.1007/s10456-013-9381-6
pubmed: 24013945
Zurlo IV, Schino M, Strippoli A, Calegari MA, Cocomazzi A, Cassano A et al (2022) Predictive value of NLR, TILs (CD4+/CD8+) and PD-L1 expression for prognosis and response to preoperative chemotherapy in gastric cancer. Cancer Immunol Immunother 71(1):45–55. https://doi.org/10.1007/s00262-021-02960-1
doi: 10.1007/s00262-021-02960-1
pubmed: 34009410
Caballero M, Sosa AE, Tagliapietra A, Grau JJ (2013) Metastatic adenoid cystic carcinoma of the salivary gland responding to cetuximab plus weekly paclitaxel after no response to weekly paclitaxel alone. Head Neck 35(2):E52–E54. https://doi.org/10.1002/hed.21870
doi: 10.1002/hed.21870
pubmed: 22144378
Hitre E, Budai B, Takácsi-Nagy Z, Rubovszky G, Tóth E, Remenár É et al (2013) Cetuximab and platinum-based chemoradio- or chemotherapy of patients with epidermal growth factor receptor expressing adenoid cystic carcinoma: a phase II trial. Br J Cancer 109(5):1117–1122. https://doi.org/10.1038/bjc.2013.468
doi: 10.1038/bjc.2013.468
pubmed: 23942070
pmcid: 3778310
Jensen AD, Krauss J, Weichert W, Debus J, Münter MW (2010) RadioImmunotherapy for adenoid cystic carcinoma: a single-institution series of combined treatment with cetuximab. Radiat Oncol 5(1):102. https://doi.org/10.1186/1748-717x-5-102
doi: 10.1186/1748-717x-5-102
pubmed: 21047402
pmcid: 2987937
Hitre E, Budai B, Takacsi-Nagy Z, Rubovszky G, Toth E, Remenar E et al (2013) Cetuximab and platinum-based chemoradio- or chemotherapy of patients with epidermal growth factor receptor expressing adenoid cystic carcinoma: a phase II trial. Br J Cancer 109(5):1117–1122. https://doi.org/10.1038/bjc.2013.468
doi: 10.1038/bjc.2013.468
pubmed: 23942070
pmcid: 3778310
Mueller SK, Haderlein M, Lettmaier S, Agaimy A, Haller F, Hecht M et al (2022) Targeted therapy, chemotherapy, immunotherapy and novel treatment options for different subtypes of salivary gland Cancer. J Clin Med 11(3):720. https://doi.org/10.3390/jcm11030720
doi: 10.3390/jcm11030720
pubmed: 35160172
pmcid: 8836387
Tchekmedyian V, Sherman EJ, Dunn L, Tran C, Baxi S, Katabi N et al (2019) Phase II study of lenvatinib in patients with progressive, recurrent or metastatic adenoid cystic carcinoma. J Clin Oncol 37(18):1529–1537. https://doi.org/10.1200/jco.18.01859
doi: 10.1200/jco.18.01859
pubmed: 30939095
pmcid: 6599407
Feeney L, Jain Y, Beasley M, Donnelly O, Kong A, Moleron R et al (2021) Centralised RECIST assessment and clinical outcomes with lenvatinib monotherapy in recurrent and metastatic adenoid cystic carcinoma. Cancers 13(17):4336. https://doi.org/10.3390/cancers13174336
doi: 10.3390/cancers13174336
pubmed: 34503145
pmcid: 8431195
Thomson DJ, Silva P, Denton K, Bonington S, Mak SK, Swindell R et al (2015) Phase II trial of sorafenib in advanced salivary adenoid cystic carcinoma of the head and neck. Head Neck 37(2):182–187. https://doi.org/10.1002/hed.23577
doi: 10.1002/hed.23577
pubmed: 24346857
Locati LD, Perrone F, Cortelazzi B, Bergamini C, Bossi P, Civelli E et al (2016) A phase II study of sorafenib in recurrent and/or metastatic salivary gland carcinomas: translational analyses and clinical impact. Eur J Cancer 69:158–165. https://doi.org/10.1016/j.ejca.2016.09.022
doi: 10.1016/j.ejca.2016.09.022
pubmed: 27821319
Locati LD, Cavalieri S, Bergamini C, Resteghini C, Alfieri S, Calareso G et al (2019) Phase II trial with axitinib in recurrent and/or metastatic salivary gland cancers of the upper aerodigestive tract. Head Neck 41(10):3670–3676. https://doi.org/10.1002/hed.25891
doi: 10.1002/hed.25891
pubmed: 31355973
Hu G, Guo M, Xu J, Wu F, Fan J, Huang Q et al (2019) Nanoparticles targeting macrophages as potential clinical therapeutic agents against cancer and inflammation. Front Immunol 10:1998. https://doi.org/10.3389/fimmu.2019.01998
doi: 10.3389/fimmu.2019.01998
pubmed: 31497026
pmcid: 6712945
Li C, Chen Q, Tian Z, Li S, Gong Z, Lin Z et al (2019) Expression of MIF, Beclin1, and LC3 in human salivary gland adenoid cystic carcinoma and its prognostic value. Medicine (Baltimore) 98(20):e15402-e. https://doi.org/10.1097/MD.0000000000015402
doi: 10.1097/MD.0000000000015402
Zhang M, Li ZF, Wang HF, Wang SS, Yu XH, Wu JB et al (2019) MIF promotes perineural invasion through EMT in salivary adenoid cystic carcinoma. Mol Carcinog 58(6):898–912. https://doi.org/10.1002/mc.22979
doi: 10.1002/mc.22979
pubmed: 30667094