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Increased tumor vascularization is associated with the amount of immune competent PD‑1 positive cells in testicular germ cell tumors

  • Authors:
    • Lukas Jennewein
    • Georg Bartsch
    • Kilian Gust
    • Hans‑Michael Kvasnicka
    • Axel Haferkamp
    • Roman Blaheta
    • Michel Mittelbronn
    • Patrick N. Harter
    • Jens Mani
  • View Affiliations / Copyright

    Affiliations: Neurological Institute (Edinger Institute), Goethe University, D‑60528 Frankfurt/Main, Germany, Department of Urology, Johannes Gutenberg University, D‑55131 Mainz, Germany, Department of Urology, Medical University of Vienna, A‑1090 Vienna, Austria, Senckenberg Institute of Pathology, Goethe University of Frankfurt/Main, D‑60590 Frankfurt/Main, Germany, Department of Urology, Goethe University, D‑60590 Frankfurt/Main, Germany, Luxembourg Centre of Neuropathology, L‑3555 Dudelange, Luxembourg
    Copyright: © Jennewein et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 9852-9860
    |
    Published online on: April 27, 2018
       https://doi.org/10.3892/ol.2018.8597
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Abstract

Testicular germ cell cancer in a metastatic state is curable with a cisplatin‑based first line chemotherapy. However, 10‑15% of these patients are resistant to first line chemotherapy and are thus left with only palliative options. Immunotherapies and inhibition of angiogenesis used in multiple types of cancer; however, the molecular context of angiogenesis and immune checkpoints in the development and progression of testicular cancers is still unknown. Therefore, the present study performed tissue micro array based analysis of 84 patients with immunohistochemistry of programmed cell death protein 1 (PD‑1), programmed cell death ligand 1 (PD‑L1) and vascular endothelial growth factor receptor 2 (VEGFR2) of testicular cancer and corresponding normal appearing testis tissue, matching the results with clinical data. The results demonstrated that PD‑L1 was significantly upregulated in testicular tumors and that PD‑1 positive cells significantly infiltrated the testicular tumor when compared with normal testicular tissue. VEGFR2 was significantly upregulated in testicular cancer. It was indicated that PD‑1 expressing cytotoxic cells may require pathologic tumor vessels to pass the blood‑testis‑barrier in order to migrate into the tumor. Notably, when matching the clinical data for PD‑1, PD‑L1 and VEGFR2 there were no differences in expression in the different International Germ Cell Cancer Collaborative Group stages of non‑seminoma. These data suggested that the anti‑PD‑1/PD‑L1 immunotherapy and the anti‑angiogenic therapy, sequentially or in combination, may be a promising option in the treatment of testicular cancer.
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View References

1 

Hanna NH and Einhorn LH: Testicular cancer-discoveries and updates. N Engl J Med. 371:2005–2016. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Mayer F, Stoop H, Scheffer GL, Scheper R, Oosterhuis JW, Looijenga LH and Bokemeyer C: Molecular determinants of treatment response in human germ cell tumors. Clin Cancer Res. 9:767–773. 2003.PubMed/NCBI

3 

Hussain SA, Ma YT, Palmer DH, Hutton P and Cullen MH: Biology of testicular germ cell tumors. Expert Rev Anticancer Ther. 8:1659–1673. 2008. View Article : Google Scholar : PubMed/NCBI

4 

Oechsle K, Honecker F, Cheng T, Mayer F, Czaykowski P, Winquist E, Wood L, Fenner M, Glaesener S, Hartmann JT, et al: Preclinical and clinical activity of sunitinib in patients with cisplatin-refractory or multiply relapsed germ cell tumors: A canadian urologic oncology group/german testicular cancer study group cooperative study. Ann Oncol. 22:2654–2660. 2011. View Article : Google Scholar : PubMed/NCBI

5 

Farkona S, Diamandis EP and Blasutig IM: Cancer immunotherapy: The beginning of the end of cancer? BMC Med. 14:732016. View Article : Google Scholar : PubMed/NCBI

6 

Sui X, Ma J, Han W, Wang X, Fang Y, Li D, Pan H and Zhang L: The anticancer immune response of anti-PD-1/PD-L1 and the genetic determinants of response to anti-PD-1/PD-L1 antibodies in cancer patients. Oncotarget. 6:19393–19404. 2015. View Article : Google Scholar : PubMed/NCBI

7 

Shi L, Chen S, Yang L and Li Y: The role of PD-1 and PD-L1 in T-cell immune suppression in patients with hematological malignancies. J Hematol Oncol. 6:742013. View Article : Google Scholar : PubMed/NCBI

8 

Escudier B, Motzer RJ, Sharma P, Wagstaff J, Plimack ER, Hammers HJ, Donskov F, Gurney H, Sosman JA, Zalewski PG, et al: Treatment beyond progression in patients with advanced renal cell carcinoma treated with nivolumab in checkmate 025. Eur Urol. 72:368–376. 2017. View Article : Google Scholar : PubMed/NCBI

9 

Mehta K, Patel K and Parikh RA: Immunotherapy in genitourinary malignancies. J Hematol Oncol. 10:952017. View Article : Google Scholar : PubMed/NCBI

10 

Gettinger SN, Horn L, Gandhi L, Spigel DR, Antonia SJ, Rizvi NA, Powderly JD, Heist RS, Carvajal RD, Jackman DM, et al: Overall survival and long-term safety of nivolumab (anti-programmed death 1 antibody, BMS-936558, ONO-4538) in patients with previously treated advanced non-small-cell lung cancer. J Clin Oncol. 33:2004–2012. 2015. View Article : Google Scholar : PubMed/NCBI

11 

Weber JS, Gibney G, Sullivan RJ, Sosman JA, Slingluff CL Jr, Lawrence DP, Logan TF, Schuchter LM, Nair S, Fecher L, et al: Sequential administration of nivolumab and ipilimumab with a planned switch in patients with advanced melanoma (CheckMate 064): An open-label, randomised, phase 2 trial. Lancet Oncol. 17:943–955. 2016. View Article : Google Scholar : PubMed/NCBI

12 

Patel SP and Kurzrock R: PD-L1 expression as a predictive biomarker in cancer immunotherapy. Mol Cancer Ther. 14:847–856. 2015. View Article : Google Scholar : PubMed/NCBI

13 

Meng X, Huang Z, Teng F, Xing L and Yu J: Predictive biomarkers in PD-1/PD-L1 checkpoint blockade immunotherapy. Cancer Treat Rev. 41:868–876. 2015. View Article : Google Scholar : PubMed/NCBI

14 

Rouhi P, Lee SL, Cao Z, Hedlund EM, Jensen LD and Cao Y: Pathological angiogenesis facilitates tumor cell dissemination and metastasis. Cell Cycle. 9:913–917. 2010. View Article : Google Scholar : PubMed/NCBI

15 

Huang Y, Yuan J, Righi E, Kamoun WS, Ancukiewicz M, Nezivar J, Santosuosso M, Martin JD, Martin MR, Vianello F, et al: Vascular normalizing doses of antiangiogenic treatment reprogram the immunosuppressive tumor microenvironment and enhance immunotherapy. Proc Natl Acad Sci USA. 109:17561–17566. 2012. View Article : Google Scholar : PubMed/NCBI

16 

Schmid MC and Varner JA: Myeloid cells in the tumor microenvironment: Modulation of tumor angiogenesis and tumor inflammation. J Oncol. 2010:2010262010. View Article : Google Scholar : PubMed/NCBI

17 

Nitzsche B, Gloesenkamp C, Schrader M, Hoffmann B, Zengerling F, Balabanov S, Honecker F and Höpfner M: Anti-tumour activity of two novel compounds in cisplatin-resistant testicular germ cell cancer. Br J Cancer. 107:1853–1863. 2012. View Article : Google Scholar : PubMed/NCBI

18 

Nitzsche B, Gloesenkamp C, Schrader M, Ocker M, Preissner R, Lein M, Zakrzewicz A, Hoffmann B and Höpfner M: Novel compounds with antiangiogenic and antiproliferative potency for growth control of testicular germ cell tumours. Br J Cancer. 103:18–28. 2010. View Article : Google Scholar : PubMed/NCBI

19 

Einstein DJ and McDermott DF: Combined blockade of vascular endothelial growth factor and programmed death 1 pathways in advanced kidney cancer. Clin Adv Hematol Oncol. 15:478–488. 2017.PubMed/NCBI

20 

International germ cell consensus classification: A prognostic factor-based staging system for metastatic germ cell cancers. International germ cell cancer collaborative group. J Clin Oncol. 15:594–603. 1997. View Article : Google Scholar : PubMed/NCBI

21 

Albers P, Albrecht W, Algaba F, Bokemeyer C, Cohn-Cedermark G, Fizazi K, Horwich A, Laguna MP, Nicolai N and Oldenburg J: EAU Guidelines Testicular Cancer. European Association of Urology. 2015.https://uroweb.org/wp-content/uploads/EAU-Guidelines-Testicular-Cancer-2016-1.pdf

22 

Baumgarten P, Harter PN, Tönjes M, Capper D, Blank AE, Sahm F, von Deimling A, Kolluru V, Schwamb B, Rabenhorst U, et al: Loss of FUBP1 expression in gliomas predicts FUBP1 mutation and is associated with oligodendroglial differentiation, IDH1 mutation and 1p/19q loss of heterozygosity. Neuropathol Appl Neurobiol. 40:205–216. 2014. View Article : Google Scholar : PubMed/NCBI

23 

Harter PN, Bernatz S, Scholz A, Zeiner PS, Zinke J, Kiyose M, Blasel S, Beschorner R, Senft C, Bender B, et al: Distribution and prognostic relevance of tumor-infiltrating lymphocytes (TILs) and PD-1/PD-L1 immune checkpoints in human brain metastases. Oncotarget. 6:40836–40849. 2015. View Article : Google Scholar : PubMed/NCBI

24 

Chovanec M, Cierna Z, Miskovska V, Machalekova K, Svetlovska D, Kalavska K, Rejlekova K, Spanik S, Kajo K, Babal P, et al: Prognostic role of programmed-death ligand 1 (PD-L1) expressing tumor infiltrating lymphocytes in testicular germ cell tumors. Oncotarget. 8:21794–21805. 2017. View Article : Google Scholar : PubMed/NCBI

25 

Cierna Z, Mego M, Miskovska V, Machalekova K, Chovanec M, Svetlovska D, Hainova K, Rejlekova K, Macak D, Spanik S, et al: Prognostic value of programmed-death-1 receptor (PD-1) and its ligand 1 (PD-L1) in testicular germ cell tumors. Ann Oncol. 27:300–305. 2016. View Article : Google Scholar : PubMed/NCBI

26 

Inaguma S, Wang Z, Lasota J, Sarlomo-Rikala M, McCue PA, Ikeda H and Miettinen M: Comprehensive immunohistochemical study of programmed cell death ligand 1 (PD-L1): Analysis in 5536 cases revealed consistent expression in trophoblastic tumors. Am J Surg Pathol. 40:1133–1142. 2016. View Article : Google Scholar : PubMed/NCBI

27 

Mansfield AS, Aubry MC, Moser JC, Harrington SM, Dronca RS, Park SS and Dong H: Temporal and spatial discordance of programmed cell death-ligand 1 expression and lymphocyte tumor infiltration between paired primary lesions and brain metastases in lung cancer. Ann Oncol. 27:1953–1958. 2016. View Article : Google Scholar : PubMed/NCBI

28 

Li CW, Lim SO, Xia W, Lee HH, Chan LC, Kuo CW, Khoo KH, Chang SS, Cha JH, Kim T, et al: Glycosylation and stabilization of programmed death ligand-1 suppresses T-cell activity. Nat Commun. 7:126322016. View Article : Google Scholar : PubMed/NCBI

29 

Miettinen M, Rikala MS, Rys J, Lasota J and Wang ZF: Vascular endothelial growth factor receptor 2 as a marker for malignant vascular tumors and mesothelioma: An immunohistochemical study of 262 vascular endothelial and 1640 nonvascular tumors. Am J Surg Pathol. 36:629–639. 2012. View Article : Google Scholar : PubMed/NCBI

30 

Holzer TR, Fulford AD, Nedderman DM, Umberger TS, Hozak RR, Joshi A, Melemed SA, Benjamin LE, Plowman GD, Schade AE, et al: Tumor cell expression of vascular endothelial growth factor receptor 2 is an adverse prognostic factor in patients with squamous cell carcinoma of the lung. PLoS One. 8:e802922013. View Article : Google Scholar : PubMed/NCBI

31 

Dellinger MT, Meadows SM, Wynne K, Cleaver O and Brekken RA: Vascular endothelial growth factor receptor-2 promotes the development of the lymphatic vasculature. PLoS One. 8:e746862013. View Article : Google Scholar : PubMed/NCBI

32 

Fanoni D, Tavecchio S, Recalcati S, Balice Y, Venegoni L, Fiorani R, Crosti C and Berti E: New monoclonal antibodies against B-cell antigens: Possible new strategies for diagnosis of primary cutaneous B-cell lymphomas. Immunol Lett. 134:157–160. 2011. View Article : Google Scholar : PubMed/NCBI

33 

Ilie M, Khambata-Ford S, Copie-Bergman C, Huang L, Juco J, Hofman V and Hofman P: Use of the 22C3 anti-PD-L1 antibody to determine PD-L1 expression in multiple automated immunohistochemistry platforms. PLoS One. 12:e01830232017. View Article : Google Scholar : PubMed/NCBI

34 

Li H and Pauza CD: CD25(+) Bcl6(low) T follicular helper cells provide help to maturing B cells in germinal centers of human tonsil. Eur J Immunol. 45:298–308. 2015. View Article : Google Scholar : PubMed/NCBI

35 

Misawa Y, Misawa K, Kawasaki H, Imai A, Mochizuki D, Ishikawa R, Endo S, Mima M, Kanazawa T, Iwashita T and Mineta H: Evaluation of epigenetic inactivation of vascular endothelial growth factor receptors in head and neck squamous cell carcinoma. Tumour Biol. 39:10104283177116572017. View Article : Google Scholar : PubMed/NCBI

36 

Solinas C, Garaud S, De Silva P, Boisson A, Van den Eynden G, de Wind A, Risso P, Vitória Rodrigues J, Richard F, Migliori E, et al: Immune checkpoint molecules on tumor-infiltrating lymphocytes and their association with tertiary lymphoid structures in human breast cancer. Front Immunol. 8:14122017. View Article : Google Scholar : PubMed/NCBI

37 

Talay O, Shen CH, Chen L and Chen J: B7-H1 (PD-L1) on T cells is required for T-cell-mediated conditioning of dendritic cell maturation. Proc Natl Acad Sci USA. 106:2741–2746. 2009. View Article : Google Scholar : PubMed/NCBI

38 

Nam-Cha SH, Roncador G, Sanchez-Verde L, Montes-Moreno S, Acevedo A, Domínguez-Franjo P and Piris MA: PD-1, a follicular T-cell marker useful for recognizing nodular lymphocyte-predominant Hodgkin lymphoma. Am J Surg Pathol. 32:1252–1257. 2008. View Article : Google Scholar : PubMed/NCBI

39 

Harter PN, Bunz B, Dietz K, Hoffmann K, Meyermann R and Mittelbronn M: Spatio-temporal deleted in colorectal cancer (DCC) and netrin-1 expression in human foetal brain development. Neuropathol Appl Neurobiol. 36:623–635. 2010. View Article : Google Scholar : PubMed/NCBI

40 

Sharma P, Callahan MK, Bono P, Kim J, Spiliopoulou P, Calvo E, Pillai RN, Ott PA, de Braud F, Morse M, et al: Nivolumab monotherapy in recurrent metastatic urothelial carcinoma (CheckMate 032): A multicentre, open-label, two-stage, multi-arm, phase 1/2 trial. Lancet Oncol. 17:1590–1598. 2016. View Article : Google Scholar : PubMed/NCBI

41 

Okazaki T and Honjo T: PD-1 and PD-1 ligands: From discovery to clinical application. Int Immunol. 19:813–824. 2007. View Article : Google Scholar : PubMed/NCBI

42 

Cheng X, Dai H, Wan N, Moore Y, Vankayalapati R and Dai Z: Interaction of programmed death-1 and programmed death-1 ligand-1 contributes to testicular immune privilege. Transplantation. 87:1778–1786. 2009. View Article : Google Scholar : PubMed/NCBI

43 

Wang LL, Li ZH, Hu XH, Muyayalo KP, Zhang YH and Liao AH: The roles of the PD-1/PD-L1 pathway at immunologically privileged sites. Am J Reprod Immunol. doi: 10.1111/aji.12710.

44 

Kaur G, Mital P and Dufour JM: Testisimmune privilege-Assumptions versus facts. Anim Reprod. 10:3–15. 2013.PubMed/NCBI

45 

Zhao S, Zhu W, Xue S and Han D: Testicular defense systems: immune privilege and innate immunity. Cell Mol Immunol. 11:428–437. 2014. View Article : Google Scholar : PubMed/NCBI

46 

Fankhauser CD, Curioni-Fontecedro A, Allmann V, Beyer J, Tischler V, Sulser T, Moch H and Bode PK: Frequent PD-L1 expression in testicular germ cell tumors. Br J Cancer. 113:411–413. 2015. View Article : Google Scholar : PubMed/NCBI

47 

Zhang Y, Kang S, Shen J, He J, Jiang L, Wang W, Guo Z, Peng G, Chen G, He J and Liang W: Prognostic significance of programmed cell death 1 (PD-1) or PD-1 ligand 1 (PD-L1) expression in epithelial-originated cancer: A meta-analysis. Medicine (Baltimore). 94:e5152015. View Article : Google Scholar : PubMed/NCBI

48 

Bentas W, Beecken WD, Glienke W, Binder J and Schuldes H: Serum levels of basic fibroblast growth factor reflect disseminated disease in patients with testicular germ cell tumors. Urol Res. 30:390–393. 2003.PubMed/NCBI

49 

Adam M, Schmidt D, Wardelmann E, Wernert N and Albers P: Angiogenetic protooncogene ets-1 induced neovascularization is involved in the metastatic process of testicular germ cell tumors. Eur Urol. 44:329–336. 2003. View Article : Google Scholar : PubMed/NCBI

50 

Subbiah V, Meric-Bernstam F, Mills GB, Shaw KR, Bailey AM, Rao P, Ward JF and Pagliaro LC: Next generation sequencing analysis of platinum refractory advanced germ cell tumor sensitive to Sunitinib (Sutent®) a VEGFR2/PDGFRβ/c-kit/FLT3/RET/CSF1R inhibitor in a phase II trial. J Hematol Oncol. 7:522014. View Article : Google Scholar : PubMed/NCBI

51 

Jones A, Fujiyama C, Turner K, Fuggle S, Cranston D, Turley H, Valtola R, Bicknell R and Harris AL: Angiogenesis and lymphangiogenesis in stage 1 germ cell tumours of the testis. BJU Int. 86:80–86. 2000. View Article : Google Scholar : PubMed/NCBI

52 

Sakai Y, Hoshino H, Kitazawa R and Kobayashi M: High endothelial venule-like vessels and lymphocyte recruitment in testicular seminoma. Andrology. 2:282–289. 2014. View Article : Google Scholar : PubMed/NCBI

53 

Carbognin L, Pilotto S, Nortilli R, Brunelli M, Nottegar A, Sperduti I, Giannarelli D, Bria E and Tortora G: Predictive and prognostic role of tumor-infiltrating lymphocytes for early breast cancer according to disease subtypes: Sensitivity analysis of randomized trials in adjuvant and neoadjuvant setting. Oncologist. 21:283–291. 2016. View Article : Google Scholar : PubMed/NCBI

54 

Turksma AW, Coupé VM, Shamier MC, Lam KL, de Weger VA, Belien JA, van den Eertwegh AJ, Meijer GA, Meijer CJ and Hooijberg E: Extent and location of tumor-infiltrating lymphocytes in microsatellite-stable colon cancer predict outcome to adjuvant active specific immunotherapy. Clin Cancer Res. 22:346–356. 2016. View Article : Google Scholar : PubMed/NCBI

55 

Yu X, Zhang Z, Wang Z, Wu P, Qiu F and Huang J: Prognostic and predictive value of tumor-infiltrating lymphocytes in breast cancer: A systematic review and meta-analysis. Clin Transl Oncol. 18:497–506. 2016. View Article : Google Scholar : PubMed/NCBI

56 

Zeng DQ, Yu YF, Ou QY, Li XY, Zhong RZ, Xie CM and Hu QG: Prognostic and predictive value of tumor-infiltrating lymphocytes for clinical therapeutic research in patients with non-small cell lung cancer. Oncotarget. 7:13765–13781. 2016. View Article : Google Scholar : PubMed/NCBI

57 

Coussens LM, Zitvogel L and Palucka AK: Neutralizing tumor-promoting chronic inflammation: A magic bullet? Science. 339:286–291. 2013. View Article : Google Scholar : PubMed/NCBI

58 

Jain RK: Normalization of tumor vasculature: An emerging concept in antiangiogenic therapy. Science. 307:58–62. 2005. View Article : Google Scholar : PubMed/NCBI

59 

Schlom J: Therapeutic cancer vaccines: Current status and moving forward. J Natl Cancer Inst. 104:599–613. 2012. View Article : Google Scholar : PubMed/NCBI

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Jennewein L, Bartsch G, Gust K, Kvasnicka HM, Haferkamp A, Blaheta R, Mittelbronn M, Harter PN and Mani J: Increased tumor vascularization is associated with the amount of immune competent PD‑1 positive cells in testicular germ cell tumors. Oncol Lett 15: 9852-9860, 2018.
APA
Jennewein, L., Bartsch, G., Gust, K., Kvasnicka, H., Haferkamp, A., Blaheta, R. ... Mani, J. (2018). Increased tumor vascularization is associated with the amount of immune competent PD‑1 positive cells in testicular germ cell tumors. Oncology Letters, 15, 9852-9860. https://doi.org/10.3892/ol.2018.8597
MLA
Jennewein, L., Bartsch, G., Gust, K., Kvasnicka, H., Haferkamp, A., Blaheta, R., Mittelbronn, M., Harter, P. N., Mani, J."Increased tumor vascularization is associated with the amount of immune competent PD‑1 positive cells in testicular germ cell tumors". Oncology Letters 15.6 (2018): 9852-9860.
Chicago
Jennewein, L., Bartsch, G., Gust, K., Kvasnicka, H., Haferkamp, A., Blaheta, R., Mittelbronn, M., Harter, P. N., Mani, J."Increased tumor vascularization is associated with the amount of immune competent PD‑1 positive cells in testicular germ cell tumors". Oncology Letters 15, no. 6 (2018): 9852-9860. https://doi.org/10.3892/ol.2018.8597
Copy and paste a formatted citation
x
Spandidos Publications style
Jennewein L, Bartsch G, Gust K, Kvasnicka HM, Haferkamp A, Blaheta R, Mittelbronn M, Harter PN and Mani J: Increased tumor vascularization is associated with the amount of immune competent PD‑1 positive cells in testicular germ cell tumors. Oncol Lett 15: 9852-9860, 2018.
APA
Jennewein, L., Bartsch, G., Gust, K., Kvasnicka, H., Haferkamp, A., Blaheta, R. ... Mani, J. (2018). Increased tumor vascularization is associated with the amount of immune competent PD‑1 positive cells in testicular germ cell tumors. Oncology Letters, 15, 9852-9860. https://doi.org/10.3892/ol.2018.8597
MLA
Jennewein, L., Bartsch, G., Gust, K., Kvasnicka, H., Haferkamp, A., Blaheta, R., Mittelbronn, M., Harter, P. N., Mani, J."Increased tumor vascularization is associated with the amount of immune competent PD‑1 positive cells in testicular germ cell tumors". Oncology Letters 15.6 (2018): 9852-9860.
Chicago
Jennewein, L., Bartsch, G., Gust, K., Kvasnicka, H., Haferkamp, A., Blaheta, R., Mittelbronn, M., Harter, P. N., Mani, J."Increased tumor vascularization is associated with the amount of immune competent PD‑1 positive cells in testicular germ cell tumors". Oncology Letters 15, no. 6 (2018): 9852-9860. https://doi.org/10.3892/ol.2018.8597
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