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Article Open Access

Modulation of PD‑L1 expression by standard therapy in head and neck cancer cell lines and exosomes

  • Authors:
    • Annette Affolter
    • Kai Liebel
    • Luisa Tengler
    • Elena Seiz
    • Moritz Tiedtke
    • Alexya Azhakesan
    • Julia Schütz
    • Marie-Nicole Theodoraki
    • Johann Kern
    • Arne M. Ruder
    • Jens Fleckenstein
    • Cleo-Aron Weis
    • Karen Bieback
    • Benedikt Kramer
    • Anne Lammert
    • Claudia Scherl
    • Nicole Rotter
    • Sonja Ludwig
  • View Affiliations / Copyright

    Affiliations: Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim of Heidelberg University, D‑68167 Mannheim, Germany, Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Ulm, D‑89075 Ulm, Germany, Department of Radiation Oncology, University Hospital Mannheim, Medical Faculty Mannheim of Heidelberg University, D‑68167 Mannheim, Germany, Department of Pathology, University Hospital Mannheim, Medical Faculty Mannheim of Heidelberg University, Mannheim, Germany, Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University, German Red Cross Blood Donor Service Baden‑Württemberg‑Hessen, D‑68167 Mannheim, Germany
    Copyright: © Affolter et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 102
    |
    Published online on: July 27, 2023
       https://doi.org/10.3892/ijo.2023.5550
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Abstract

Although checkpoint inhibitors (CPI) have recently extended the treatment options and improved clinical response of advanced stage head and neck squamous cell carcinoma (HNSCC), treatment success remains unpredictable. Programmed cell death ligand‑1 (PD‑L1) is a key player in immunotherapy. Tumor cells, and exosomes derived therefrom, are carriers of PD‑L1 and efficiently suppress immune responses. The aim of the present study was to analyze the influence of established therapies on PD‑L1 expression of HNSCC cell lines and their exosomes. The HNSCC cell lines, UM‑SCC‑11B, UM‑SCC‑14C and UM‑SCC‑22C were treated with fractionated radiotherapy (RT; 5x2 Gy), cisplatin (CT) and cetuximab (Cetux) as monotherapy, or combined therapy, chemoradiotherapy (CRT; RT and CT) or radioimmunotherapy (RT and Cetux). The expression of PD‑L1 and phosphorylated (p)ERK1/2 as a mediator of radioresistance were assessed using western blotting, immunohistochemistry and an ex vivo vital tissue culture model. Additionally, exosomes were isolated from concentrated supernatants of the (un‑)treated HNSCC cell lines by size exclusion chromatography. Exosomal protein expression levels of PD‑L1 were detected using western blotting and semi‑quantitative levels were calculated. The functional impact of exosomes from the (un‑)treated HNSCC cell lines on the proliferation (MTS assay) and apoptosis (Caspase 3/7 assay) of the untreated HNSCC cell lines were measured and compared. The HNSCC cell lines UM‑SCC‑11B and UM‑SCC‑22B showed strong expression of pERK1/2 and PD‑L1, respectively. RT upregulated the PD‑L1 expression in UM‑SCC‑11B and UM‑SCC‑14C and in exosomes from all three cell lines. CT alone induced PD‑L1 expression in all cell lines. CRT induced the expression of PD‑L1 in all HNSCC cell lines and exosomes from UM‑SCC‑14C and UM‑SCC‑22B. The data indicated a potential co‑regulation of PD‑L1 and activated ERK1/2, most evident in UM‑SCC‑14C. Exosomes from irradiated UM‑SCC‑14C cells protected the unirradiated cells from apoptosis by Caspase 3/7 downregulation. The present study suggested a tumor cell‑mediated regulation of PD‑L1 upon platinum‑based CRT in HNSCC and in exosomes. A co‑regulation of PD‑L1 and MAPK signaling response was hypothesized.
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View References

1 

Sacco AG and Cohen EE: Current treatment options for recurrent or metastatic head and neck squamous cell carcinoma. J Clin Oncol. 33:3305–3313. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Burtness B, Harrington KJ, Greil R, Soulières D, Tahara M, de Castro G Jr, Psyrri A, Basté N, Neupane P, Bratland Å, et al: Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): A randomised, open-label, phase 3 study. Lancet. 394:1915–1928. 2019. View Article : Google Scholar : PubMed/NCBI

3 

Gillison ML, Blumenschein G Jr, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington KJ, Kasper S, Vokes EE, Even C, et al: CheckMate 141: 1-Year update and subgroup analysis of nivolumab as first-line therapy in patients with recurrent/metastatic head and neck cancer. Oncologist. 23:1079–1082. 2018. View Article : Google Scholar : PubMed/NCBI

4 

Pardoll DM: The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 12:252–264. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Sun C, Mezzadra R and Schumacher TN: Regulation and function of the PD-L1 checkpoint. Immunity. 48:434–452. 2018. View Article : Google Scholar : PubMed/NCBI

6 

Pai SI, Zandberg DP and Strome SE: The role of antagonists of the PD-1:PD-L1/PD-L2 axis in head and neck cancer treatment. Oral Oncol. 61:152–158. 2016. View Article : Google Scholar : PubMed/NCBI

7 

Keck MK, Zuo Z, Khattri A, Stricker TP, Brown CD, Imanguli M, Rieke D, Endhardt K, Fang P, Brägelmann J, et al: Integrative analysis of head and neck cancer identifies two biologically distinct HPV and three non-HPV subtypes. Clin Cancer Res. 21:870–881. 2015. View Article : Google Scholar

8 

Seiwert TY, Burtness B, Mehra R, Weiss J, Berger R, Eder JP, Heath K, McClanahan T, Lunceford J, Gause C, et al: Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): An open-label, multicentre, phase 1b trial. Lancet Oncol. 17:956–965. 2016. View Article : Google Scholar : PubMed/NCBI

9 

Chow LQM, Haddad R, Gupta S, Mahipal A, Mehra R, Tahara M, Berger R, Eder JP, Burtness B, Lee SH, et al: Antitumor activity of pembrolizumab in biomarker-unselected patients with recurrent and/or metastatic head and neck squamous cell carcinoma: Results from the phase Ib KEYNOTE-012 expansion cohort. J Clin Oncol. 34:3838–3845. 2016. View Article : Google Scholar : PubMed/NCBI

10 

Soulieres D, Cohen E, Le Tourneau C, Dinis J, Licitra L, Ahn MJ, Soria A, Machiels JP, Mach N, Mehra R, et al: Abstract CT115: Updated survival results of the KEYNOTE-040 study of pembrolizumab vs standard-of-care chemotherapy for recurrent or metastatic head and neck squamous cell carcinoma. Cancer Res. 78(13 Suppl): CT1152018. View Article : Google Scholar

11 

Ferris RL, Blumenschein G Jr, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington K, Kasper S, Vokes EE, Even C, et al: Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med. 375:1856–1867. 2016. View Article : Google Scholar

12 

Gavrielatou N, Doumas S, Economopoulou P, Foukas PG and Psyrri A: Biomarkers for immunotherapy response in head and neck cancer. Cancer Treat Rev. 84:1019772020. View Article : Google Scholar : PubMed/NCBI

13 

Ludwig S, Floros T, Theodoraki MN, Hong CS, Jackson EK, Lang S and Whiteside TL: Suppression of lymphocyte functions by plasma exosomes correlates with disease activity in patients with head and neck cancer. Clin Cancer Res. 23:4843–4854. 2017. View Article : Google Scholar : PubMed/NCBI

14 

Cocucci E and Meldolesi J: Ectosomes and exosomes: Shedding the confusion between extracellular vesicles. Trends Cell Biol. 25:364–372. 2015. View Article : Google Scholar : PubMed/NCBI

15 

van der Pol E, Böing AN, Harrison P, Sturk A and Nieuwland R: Classification, functions, and clinical relevance of extracellular vesicles. Pharmacol Rev. 64:676–705. 2012. View Article : Google Scholar : PubMed/NCBI

16 

Ludwig S, Sharma P, Wise P, Sposto R, Hollingshead D, Lamb J, Lang S, Fabbri M and Whiteside TL: mRNA and miRNA profiles of exosomes from cultured tumor cells reveal biomarkers specific for HPV16-positive and HPV16-negative head and neck cancer. Int J Mol Sci. 21:85702020. View Article : Google Scholar : PubMed/NCBI

17 

Ludwig S, Marczak L, Sharma P, Abramowicz A, Gawin M, Widlak P, Whiteside TL and Pietrowska M: Proteomes of exosomes from HPV(+) or HPV(-) head and neck cancer cells: Differential enrichment in immunoregulatory proteins. Oncoimmunology. 8:15938082019. View Article : Google Scholar : PubMed/NCBI

18 

Theodoraki MN, Yerneni SS, Hoffmann TK, Gooding WE and Whiteside TL: Clinical significance of PD-L1+ exosomes in plasma of head and neck cancer patients. Clin Cancer Res. 24:896–905. 2018. View Article : Google Scholar

19 

Theodoraki MN, Laban S, Jackson EK, Lotfi R, Schuler PJ, Brunner C, Hoffmann TK, Whiteside TL and Hofmann L: Changes in circulating exosome molecular profiles following surgery/(chemo)radiotherapy: Early detection of response in head and neck cancer patients. Br J Cancer. 125:1677–1686. 2021. View Article : Google Scholar : PubMed/NCBI

20 

Jablonska J, Rist M, Spyra I, Tengler L, Domnich M, Kansy B, Giebel B, Thakur BK, Rotter N, Lang S and Ludwig S: Evaluation of immunoregulatory biomarkers on plasma small extracellular vesicles for disease progression and early therapeutic response in head and neck cancer. Cells. 11:9022022. View Article : Google Scholar : PubMed/NCBI

21 

Daassi D, Mahoney KM and Freeman GJ: The importance of exosomal PDL1 in tumour immune evasion. Nat Rev Immunol. 20:209–215. 2020. View Article : Google Scholar : PubMed/NCBI

22 

Gandara DR, Paul SM, Kowanetz M, Schleifman E, Zou W, Li Y, Rittmeyer A, Fehrenbacher L, Otto G, Malboeuf C, et al: Blood-based tumor mutational burden as a predictor of clinical benefit in non-small-cell lung cancer patients treated with atezolizumab. Nat Med. 24:1441–1448. 2018. View Article : Google Scholar : PubMed/NCBI

23 

Rückert M, Flohr AS, Hecht M and Gaipl US: Radiotherapy and the immune system: More than just immune suppression. Stem Cells. 39:1155–1165. 2021. View Article : Google Scholar : PubMed/NCBI

24 

Hecht M, Fietkau R and Gaipl US: Definitive chemoradiotherapy of locally advanced head and neck cancer in combination with immune checkpoint inhibition-new concepts required. Strahlenther Onkol. 198:83–85. 2022.In German. View Article : Google Scholar

25 

Welters MJ, Fichtinger-Schepman AM, Baan RA, Hermsen MA, van der Vijgh WJ, Cloos J and Braakhuis BJ: Relationship between the parameters cellular differentiation, doubling time and platinum accumulation and cisplatin sensitivity in a panel of head and neck cancer cell lines. Int J Cancer. 71:410–415. 1997. View Article : Google Scholar : PubMed/NCBI

26 

Affolter A, Muller MF, Sommer K, Stenzinger A, Zaoui K, Lorenz K, Wolf T, Sharma S, Wolf J, Perner S, et al: Targeting irradiation-induced mitogen-activated protein kinase activation in vitro and in an ex vivo model for human head and neck cancer. Head Neck. 38(Suppl 1): E2049–E2061. 2016. View Article : Google Scholar : PubMed/NCBI

27 

Hong CS, Funk S, Muller L, Boyiadzis M and Whiteside TL: Isolation of biologically active and morphologically intact exosomes from plasma of patients with cancer. J Extracell Vesicles. 5:292892016. View Article : Google Scholar : PubMed/NCBI

28 

Rajamoorthi A, Shrivastava S, Steele R, Nerurkar P, Gonzalez JG, Crawford S, Varvares M and Ray RB: Bitter melon reduces head and neck squamous cell carcinoma growth by targeting c-Met signaling. PLoS One. 8:e780062013. View Article : Google Scholar : PubMed/NCBI

29 

Chu SC, Hsieh YS, Yu CC, Lai YY and Chen PN: Thymoquinone induces cell death in human squamous carcinoma cells via caspase activation-dependent apoptosis and LC3-II activation-dependent autophagy. PLoS One. 9:e1015792014. View Article : Google Scholar : PubMed/NCBI

30 

Chien MH, Yang WE, Yang YC, Ku CC, Lee WJ, Tsai MY, Lin CW and Yang SF: Dual targeting of the p38 MAPK-HO-1 axis and cIAP1/XIAP by demethoxycurcumin triggers caspase-mediated apoptotic cell death in oral squamous cell carcinoma cells. Cancers (Basel). 12:7032020. View Article : Google Scholar : PubMed/NCBI

31 

Chung EJ, Brown AP, Asano H, Mandler M, Burgan WE, Carter D, Camphausen K and Citrin D: In vitro and in vivo radio-sensitization with AZD6244 (ARRY-142886), an inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 kinase. Clin Cancer Res. 15:3050–3057. 2009. View Article : Google Scholar : PubMed/NCBI

32 

Leiker AJ, DeGraff W, Choudhuri R, Sowers AL, Thetford A, Cook JA, Van Waes C and Mitchell JB: Radiation enhancement of head and neck squamous cell carcinoma by the dual PI3K/mTOR inhibitor PF-05212384. Clin Cancer Res. 21:2792–2801. 2015. View Article : Google Scholar : PubMed/NCBI

33 

Affolter A, Drigotas M, Fruth K, Schmidtmann I, Brochhausen C, Mann WJ and Brieger J: Increased radioresistance via G12S K-Ras by compensatory upregulation of MAPK and PI3K pathways in epithelial cancer. Head Neck. 35:220–228. 2013. View Article : Google Scholar

34 

Affolter A, Fruth K, Brochhausen C, Schmidtmann I, Mann WJ and Brieger J: Activation of mitogen-activated protein kinase extracellular signal-related kinase in head and neck squamous cell carcinomas after irradiation as part of a rescue mechanism. Head Neck. 33:1448–1457. 2011. View Article : Google Scholar : PubMed/NCBI

35 

Affolter A, Samosny G, Heimes AS, Schneider J, Weichert W, Stenzinger A, Sommer K, Jensen A, Mayer A, Brenner W, et al: Multikinase inhibitors sorafenib and sunitinib as radiosensitizers in head and neck cancer cell lines. Head Neck. 39:623–632. 2017. View Article : Google Scholar : PubMed/NCBI

36 

Théry C, Witwer KW, Aikawa E, Alcaraz MJ, Anderson JD, Andriantsitohaina R, Antoniou A, Arab T, Archer F, Atkin-Smith GK, et al: Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the international society for extracellular vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles. 7:15357502018. View Article : Google Scholar

37 

Ock CY, Kim S, Keam B, Kim S, Ahn YO, Chung EJ, Kim JH, Kim TM, Kwon SK, Jeon YK, et al: Changes in programmed death-ligand 1 expression during cisplatin treatment in patients with head and neck squamous cell carcinoma. Oncotarget. 8:97920–97927. 2017. View Article : Google Scholar : PubMed/NCBI

38 

Barker HE, Paget JTE, Khan AA and Harrington KJ: The tumour microenvironment after radiotherapy: Mechanisms of resistance and recurrence. Nat Rev Cancer. 15:409–425. 2015. View Article : Google Scholar : PubMed/NCBI

39 

Dovedi SJ, Adlard AL, Lipowska-Bhalla G, McKenna C, Jones S, Cheadle EJ, Stratford IJ, Poon E, Morrow M, Stewart R, et al: Acquired resistance to fractionated radiotherapy can be overcome by concurrent PD-L1 blockade. Cancer Res. 74:5458–5468. 2014. View Article : Google Scholar : PubMed/NCBI

40 

Hirsch L, Zitvogel L, Eggermont A and Marabelle A: PD-Loma: A cancer entity with a shared sensitivity to the PD-1/PD-L1 pathway blockade. Br J Cancer. 120:3–5. 2019. View Article : Google Scholar :

41 

Kong Y, Ma Y, Zhao X, Pan J, Xu Z and Zhang L: Optimizing the treatment schedule of radiotherapy combined with anti-PD-1/PD-L1 immunotherapy in metastatic cancers. Front Oncol. 11:6388732021. View Article : Google Scholar : PubMed/NCBI

42 

Narits J, Tamm H and Jaal J: PD-L1 induction in tumor tissue after hypofractionated thoracic radiotherapy for non-small cell lung cancer. Clin Transl Radiat Oncol. 22:83–87. 2020. View Article : Google Scholar : PubMed/NCBI

43 

Kordbacheh T, Honeychurch J, Blackhall F, Faivre-Finn C and Illidge T: Radiotherapy and anti-PD-1/PD-L1 combinations in lung cancer: Building better translational research platforms. Ann Oncol. 29:301–310. 2018. View Article : Google Scholar : PubMed/NCBI

44 

Wimmer S, Deloch L, Hader M, Derer A, Grottker F, Weissmann T, Hecht M, Gostian AO, Fietkau R, Frey B and Gaipl US: Hypofractionated radiotherapy upregulates several immune checkpoint molecules in head and neck squamous cell carcinoma cells independently of the HPV status while ICOS-L is upregulated only on HPV-positive cells. Int J Mol Sci. 22:91142021. View Article : Google Scholar : PubMed/NCBI

45 

Kikuchi M, Clump DA, Srivastava RM, Sun L, Zeng D, Diaz-Perez JA, Anderson CJ, Edwards WB and Ferris RL: Preclinical immunoPET/CT imaging using Zr-89-labeled anti-PD-L1 monoclonal antibody for assessing radiation-induced PD-L1 upregulation in head and neck cancer and melanoma. Oncoimmunology. 6:e13290712017. View Article : Google Scholar : PubMed/NCBI

46 

Schulz D, Stancev I, Sorrentino A, Menevse AN, Beckhove P, Brockhoff G, Hautmann MG, Reichert TE, Bauer RJ and Ettl T: Increased PD-L1 expression in radioresistant HNSCC cell lines after irradiation affects cell proliferation due to inactivation of GSK-3beta. Oncotarget. 10:573–583. 2019. View Article : Google Scholar : PubMed/NCBI

47 

Mutschelknaus L, Peters C, Winkler K, Yentrapalli R, Heider T, Atkinson MJ and Moertl S: Exosomes derived from squamous head and neck cancer promote cell survival after ionizing radiation. PLoS One. 11:e01522132016. View Article : Google Scholar : PubMed/NCBI

48 

Taube JM, Klein A, Brahmer JR, Xu H, Pan X, Kim JH, Chen L, Pardoll DM, Topalian SL and Anders RA: Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy. Clin Cancer Res. 20:5064–5074. 2014. View Article : Google Scholar : PubMed/NCBI

49 

Snyder A, Makarov V, Merghoub T, Yuan J, Zaretsky JM, Desrichard A, Walsh LA, Postow MA, Wong P, Ho TS, et al: Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med. 371:2189–2199. 2014. View Article : Google Scholar : PubMed/NCBI

50 

Ribas A and Hu-Lieskovan S: What does PD-L1 positive or negative mean? J Exp Med. 213:2835–2840. 2016. View Article : Google Scholar : PubMed/NCBI

51 

Derer A, Spiljar M, Bäumler M, Hecht M, Fietkau R, Frey B and Gaipl US: Chemoradiation increases PD-L1 expression in certain melanoma and glioblastoma cells. Front Immunol. 7:6102016. View Article : Google Scholar

52 

Oweida A, Lennon S, Calame D, Korpela S, Bhatia S, Sharma J, Graham C, Binder D, Serkova N, Raben D, et al: Ionizing radiation sensitizes tumors to PD-L1 immune checkpoint blockade in orthotopic murine head and neck squamous cell carcinoma. Oncoimmunology. 6:e13561532017. View Article : Google Scholar : PubMed/NCBI

53 

Deng L, Liang H, Burnette B, Beckett M, Darga T, Weichselbaum RR and Fu YX: Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice. J Clin Invest. 124:687–695. 2014. View Article : Google Scholar : PubMed/NCBI

54 

Zhang B, Bowerman NA, Salama JK, Schmidt H, Spiotto MT, Schietinger A, Yu P, Fu YX, Weichselbaum RR, Rowley DA, et al: Induced sensitization of tumor stroma leads to eradication of established cancer by T cells. J Exp Med. 204:49–55. 2007. View Article : Google Scholar : PubMed/NCBI

55 

Lin W, Chen M, Hong L, Zhao H and Chen Q: Crosstalk between PD-1/PD-L1 blockade and its combinatorial therapies in tumor immune microenvironment: A focus on HNSCC. Front Oncol. 8:5322018. View Article : Google Scholar : PubMed/NCBI

56 

Rossi G, Russo A, Tagliamento M, Tuzi A, Nigro O, Vollome G Sini C, Grassi M, Bello MGD, Coco S, et al: Präzisionsmedizin bei NSCLC im zeitalter der immuntherapie: Neue biomarker zur selektion der am besten geeigneten therapie oder des am besten geeigneten patienten. Kompass Pneumol. 8:300–317. 2020. View Article : Google Scholar

57 

Müller T, Braun M, Dietrich D, Aktekin S, Höft S, Kristiansen G, Göke F, Schröck A, Brägelmann J, Held SAE, et al: PD-L1: A novel prognostic biomarker in head and neck squamous cell carcinoma. Oncotarget. 8:52889–52900. 2017. View Article : Google Scholar : PubMed/NCBI

58 

Balermpas P, Rödel F, Krause M, Linge A, Lohaus F, Baumann M, Tinhofer I, Budach V, Sak A, Stuschke M, et al: The PD-1/PD-L1 axis and human papilloma virus in patients with head and neck cancer after adjuvant chemoradiotherapy: A multicentre study of the German cancer consortium radiation oncology group (DKTK-ROG). Int J Cancer. 141:594–603. 2017. View Article : Google Scholar : PubMed/NCBI

59 

Hong AM, Ferguson P, Dodds T, Jones D, Li M, Yang J and Scolyer RA: Significant association of PD-L1 expression with human papillomavirus positivity and its prognostic impact in oropharyngeal cancer. Oral Oncol. 92:33–39. 2019. View Article : Google Scholar : PubMed/NCBI

60 

Chen G, Huang AC, Zhang W, Zhang G, Wu M, Xu W, Yu Z, Yang J, Wang B, Sun H, et al: Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response. Nature. 560:382–386. 2018. View Article : Google Scholar : PubMed/NCBI

61 

Cordonnier M, Nardin C, Chanteloup G, Derangere V, Algros MP, Arnould L, Garrido C, Aubin F and Gobbo J: Tracking the evolution of circulating exosomal-PD-L1 to monitor melanoma patients. J Extracell Vesicles. 9:17108992020. View Article : Google Scholar : PubMed/NCBI

62 

da Silva JL, Dos Santos ALS, Nunes NCC, de Moraes Lino da Silva F, Ferreira CGM and de Melo AC: Cancer immunotherapy: The art of targeting the tumor immune microenvironment. Cancer Chemother Pharmacol. 84:227–240. 2019. View Article : Google Scholar : PubMed/NCBI

63 

Theodoraki MN, Yerneni S, Gooding WE, Ohr J, Clump DA, Bauman JE, Ferris RL and Whiteside TL: Circulating exosomes measure responses to therapy in head and neck cancer patients treated with cetuximab, ipilimumab, and IMRT. Oncoimmunology. 8:15938052019. View Article : Google Scholar : PubMed/NCBI

64 

Ota K, Azuma K, Kawahara A, Hattori S, Iwama E, Tanizaki J, Harada T, Matsumoto K, Takayama K, Takamori S, et al: Induction of PD-L1 expression by the EML4-ALK oncoprotein and downstream signaling pathways in non-small cell lung cancer. Clin Cancer Res. 21:4014–4021. 2015. View Article : Google Scholar : PubMed/NCBI

65 

Han JJ, Kim DW, Koh J, Keam B, Kim TM, Jeon YK, Lee SH, Chung DH and Heo DS: Change in PD-L1 expression after acquiring resistance to gefitinib in EGFR-mutant non-small-cell lung cancer. Clin Lung Cancer. 17:263–270.e2. 2016. View Article : Google Scholar

66 

Ebert PJR, Cheung J, Yang Y, McNamara E, Hong R, Moskalenko M, Gould SE, Maecker H, Irving BA, Kim JM, et al: MAP kinase inhibition promotes T cell and anti-tumor activity in combination with PD-L1 checkpoint blockade. Immunity. 44:609–621. 2016. View Article : Google Scholar : PubMed/NCBI

67 

Jiang X, Zhou J, Giobbie-Hurder A, Wargo J and Hodi FS: The activation of MAPK in melanoma cells resistant to BRAF inhibition promotes PD-L1 expression that is reversible by MEK and PI3K inhibition. Clin Cancer Res. 19:598–609. 2013. View Article : Google Scholar

68 

Derer A, Frey B, Fietkau R and Gaipl US: Immune-modulating properties of ionizing radiation: Rationale for the treatment of cancer by combination radiotherapy and immune checkpoint inhibitors. Cancer Immunol Immunother. 65:779–786. 2016. View Article : Google Scholar

69 

Burnette BC, Liang H, Lee Y, Chlewicki L, Khodarev NN, Weichselbaum RR, Fu YX and Auh SL: The efficacy of radiotherapy relies upon induction of type I interferon-dependent innate and adaptive immunity. Cancer Res. 71:2488–2496. 2011. View Article : Google Scholar : PubMed/NCBI

70 

Lee Y, Auh SL, Wang Y, Burnette B, Wang Y, Meng Y, Beckett M, Sharma R, Chin R, Tu T, et al: Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment. Blood. 114:589–595. 2009. View Article : Google Scholar : PubMed/NCBI

71 

Lugade AA, Moran JP, Gerber SA, Rose RC, Frelinger JG and Lord EM: Local radiation therapy of B16 melanoma tumors increases the generation of tumor antigen-specific effector cells that traffic to the tumor. J Immunol. 174:7516–7523. 2005. View Article : Google Scholar : PubMed/NCBI

72 

Dewan MZ, Galloway AE, Kawashima N, Dewyngaert JK, Babb JS, Formenti SC and Demaria S: Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody. Clin Cancer Res. 15:5379–5388. 2009. View Article : Google Scholar : PubMed/NCBI

73 

Rong C, Muller MF, Xiang F, Jensen A, Weichert W, Major G, Plinkert PK, Hess J and Affolter A: Adaptive ERK signalling activation in response to therapy and in silico prognostic evaluation of EGFR-MAPK in HNSCC. Br J Cancer. 123:288–297. 2020. View Article : Google Scholar : PubMed/NCBI

74 

Fournel L, Wu Z, Stadler N, Damotte D, Lococo F, Boulle G, Ségal-Bendirdjian E, Bobbio A, Icard P, Trédaniel J, et al: Cisplatin increases PD-L1 expression and optimizes immune check-point blockade in non-small cell lung cancer. Cancer Lett. 464:5–14. 2019. View Article : Google Scholar : PubMed/NCBI

75 

Park SJ, Ye W, Xiao R, Silvin C, Padget M, Hodge JW, Van Waes C and Schmitt NC: Cisplatin and oxaliplatin induce similar immunogenic changes in preclinical models of head and neck cancer. Oral Oncol. 95:127–135. 2019. View Article : Google Scholar : PubMed/NCBI

76 

Tran L, Allen CT, Xiao R, Moore E, Davis R, Park SJ, Spielbauer K, Van Waes C and Schmitt NC: Cisplatin alters antitumor immunity and synergizes with PD-1/PD-L1 inhibition in head and neck squamous cell carcinoma. Cancer Immunol Res. 5:1141–1151. 2017. View Article : Google Scholar : PubMed/NCBI

77 

Varayathu H, Sarathy V, Thomas BE, Mufti SS and Naik R: Combination strategies to augment immune check point inhibitors efficacy-implications for translational research. Front Oncol. 11:5591612021. View Article : Google Scholar

78 

Califano JA, Khan Z, Noonan KA, Rudraraju L, Zhang Z, Wang H, Goodman S, Gourin CG, Ha PK, Fakhry C, et al: Tadalafil augments tumor specific immunity in patients with head and neck squamous cell carcinoma. Clin Cancer Res. 21:30–38. 2015. View Article : Google Scholar : PubMed/NCBI

79 

Merlano MC, Merlotti AM, Licitra L, Denaro N, Fea E, Galizia D, Di Maio M, Fruttero C, Curcio P, Vecchio S, et al: Activation of immune responses in patients with relapsed-metastatic head and neck cancer (CONFRONT phase I-II trial): Multimodality immunotherapy with avelumab, short-course radiotherapy, and cyclophosphamide. Clin Transl Radiat Oncol. 12:47–52. 2018. View Article : Google Scholar : PubMed/NCBI

80 

Kim JE, Patel MA, Mangraviti A, Kim ES, Theodros D, Velarde E, Liu A, Sankey EW, Tam A, Xu H, et al: Combination therapy with anti-PD-1, anti-TIM-3, and focal radiation results in regression of murine gliomas. Clin Cancer Res. 23:124–136. 2017. View Article : Google Scholar :

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Copy and paste a formatted citation
Spandidos Publications style
Affolter A, Liebel K, Tengler L, Seiz E, Tiedtke M, Azhakesan A, Schütz J, Theodoraki M, Kern J, Ruder AM, Ruder AM, et al: Modulation of PD‑L1 expression by standard therapy in head and neck cancer cell lines and exosomes. Int J Oncol 63: 102, 2023.
APA
Affolter, A., Liebel, K., Tengler, L., Seiz, E., Tiedtke, M., Azhakesan, A. ... Ludwig, S. (2023). Modulation of PD‑L1 expression by standard therapy in head and neck cancer cell lines and exosomes. International Journal of Oncology, 63, 102. https://doi.org/10.3892/ijo.2023.5550
MLA
Affolter, A., Liebel, K., Tengler, L., Seiz, E., Tiedtke, M., Azhakesan, A., Schütz, J., Theodoraki, M., Kern, J., Ruder, A. M., Fleckenstein, J., Weis, C., Bieback, K., Kramer, B., Lammert, A., Scherl, C., Rotter, N., Ludwig, S."Modulation of PD‑L1 expression by standard therapy in head and neck cancer cell lines and exosomes". International Journal of Oncology 63.3 (2023): 102.
Chicago
Affolter, A., Liebel, K., Tengler, L., Seiz, E., Tiedtke, M., Azhakesan, A., Schütz, J., Theodoraki, M., Kern, J., Ruder, A. M., Fleckenstein, J., Weis, C., Bieback, K., Kramer, B., Lammert, A., Scherl, C., Rotter, N., Ludwig, S."Modulation of PD‑L1 expression by standard therapy in head and neck cancer cell lines and exosomes". International Journal of Oncology 63, no. 3 (2023): 102. https://doi.org/10.3892/ijo.2023.5550
Copy and paste a formatted citation
x
Spandidos Publications style
Affolter A, Liebel K, Tengler L, Seiz E, Tiedtke M, Azhakesan A, Schütz J, Theodoraki M, Kern J, Ruder AM, Ruder AM, et al: Modulation of PD‑L1 expression by standard therapy in head and neck cancer cell lines and exosomes. Int J Oncol 63: 102, 2023.
APA
Affolter, A., Liebel, K., Tengler, L., Seiz, E., Tiedtke, M., Azhakesan, A. ... Ludwig, S. (2023). Modulation of PD‑L1 expression by standard therapy in head and neck cancer cell lines and exosomes. International Journal of Oncology, 63, 102. https://doi.org/10.3892/ijo.2023.5550
MLA
Affolter, A., Liebel, K., Tengler, L., Seiz, E., Tiedtke, M., Azhakesan, A., Schütz, J., Theodoraki, M., Kern, J., Ruder, A. M., Fleckenstein, J., Weis, C., Bieback, K., Kramer, B., Lammert, A., Scherl, C., Rotter, N., Ludwig, S."Modulation of PD‑L1 expression by standard therapy in head and neck cancer cell lines and exosomes". International Journal of Oncology 63.3 (2023): 102.
Chicago
Affolter, A., Liebel, K., Tengler, L., Seiz, E., Tiedtke, M., Azhakesan, A., Schütz, J., Theodoraki, M., Kern, J., Ruder, A. M., Fleckenstein, J., Weis, C., Bieback, K., Kramer, B., Lammert, A., Scherl, C., Rotter, N., Ludwig, S."Modulation of PD‑L1 expression by standard therapy in head and neck cancer cell lines and exosomes". International Journal of Oncology 63, no. 3 (2023): 102. https://doi.org/10.3892/ijo.2023.5550
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