Current Oncology Reports

, Volume 13, Issue 6, pp 488–497

Immunobiology of Merkel Cell Carcinoma: Implications for Immunotherapy of a Polyomavirus-Associated Cancer

Melanoma (Kim Margolin, Section Editor)


Merkel cell carcinoma (MCC) is an aggressive skin malignancy with a high mortality rate and an increasing incidence. The recent discovery of Merkel cell polyomavirus has revolutionized our understanding of MCC pathogenesis. Viral oncoproteins appear to play a critical role in tumor progression and are expressed in the majority of MCC tumors. Virus-specific humoral and cellular immune responses are detectable in MCC patients and are linked to the natural history of the disease. Despite persistent expression of immunogenic viral proteins, however, MCC tumors are able to evade the immune system. Understanding of the mechanisms of immune evasion employed by MCC tumors is rapidly increasing and offers opportunities for development of rational immune therapies to improve patient outcomes. Here we review recent discoveries in MCC with a special focus on the pathogenic role of Merkel cell polyomavirus and the immunobiology of this virus-associated disease.


Merkel cell carcinoma Immunotherapy Merkel cell polyomavirus MCV MCPyV Cancer virus Viral cancer Immune evasion Immune escape MHC Tumor immunology Tumor infiltrating lymphocytes TILs Viral oncoproteins T-antigen Immune suppression 


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    • Lemos BD, Storer, BE, Iyer, JG, et al.: Pathologic nodal evaluation improves prognostic accuracy in Merkel cell carcinoma: analysis of 5,823 cases as the basis of the first consensus staging system for this cancer. J Am Acad Dermatol. 2010. A publication especially relevant to the clinician, as it determines the prognostic significance of tumor size, clinical versus pathologic nodal evaluation, and extent of disease at presentation and thereby derives the first consensus staging/prognostic system for MCC. Google Scholar
  2. 2.
    Lemos B, Nghiem P. Merkel cell carcinoma: more deaths but still no pathway to blame. J Invest Dermatol. 2007;127:2100–3.PubMedCrossRefGoogle Scholar
  3. 3.
    Albores-Saavedra J, Batich, K, Chable-Montero, F, et al.: Merkel cell carcinoma demographics, morphology, and survival based on 3870 cases: a population based study. J Cutan Pathol. 2009.Google Scholar
  4. 4.
    Hodgson NC. Merkel cell carcinoma: changing incidence trends. J Surg Oncol. 2005;89:1–4.PubMedCrossRefGoogle Scholar
  5. 5.
    Moll R, Löwe A, Laufer J, Franke WW. Cytokeratin 20 in human carcinomas. A new histodiagnostic marker detected by monoclonal antibodies. Am J Pathol. 1992;140:427–47.PubMedGoogle Scholar
  6. 6.
    Heath M, Jaimes N, Lemos B, et al. Clinical characteristics of Merkel cell carcinoma at diagnosis in 195 patients: the AEIOU features. J Am Acad Dermatol. 2008;58:375–81.PubMedCrossRefGoogle Scholar
  7. 7.
    Weinstock MA, Gardstein B. Twenty-year trends in the reported incidence of mycosis fungoides and associated mortality. Am J Publ Health. 1999;89:1240–4.CrossRefGoogle Scholar
  8. 8.
    American Cancer Society. Cancer facts & figures 2006. Atlanta: American Cancer Society; 2006.Google Scholar
  9. 9.
    Tai PT, Yu E, Winquist E, et al. Chemotherapy in neuroendocrine/Merkel cell carcinoma of the skin: case series and review of 204 cases. J Clin Oncol. 2000;18:2493–9.PubMedGoogle Scholar
  10. 10.
    Penn I. Posttransplant malignancies. Transplant Proc. 1999;31:1260–2.PubMedCrossRefGoogle Scholar
  11. 11.
    Agelli M, Clegg LX. Epidemiology of primary Merkel cell carcinoma in the United States. J Am Acad Dermatol. 2003;49:832–41.PubMedCrossRefGoogle Scholar
  12. 12.
    Engels EA, Frisch M, Goedert JJ, et al. Merkel cell carcinoma and HIV infection. Lancet. 2002;359:497–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Burack J, Altschuler EL. Sustained remission of metastatic Merkel cell carcinoma with treatment of HIV infection. J R Soc Med. 2003;96:238–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Muirhead R, Ritchie DM. Partial regression of Merkel cell carcinoma in response to withdrawal of azathioprine in an immunosuppression-induced case of metastatic Merkel cell carcinoma. Clin Oncol (R Coll Radiol). 2007;19.Google Scholar
  15. 15.
    Miller RW, Rabkin CS. Merkel cell carcinoma and melanoma: etiological similarities and differences. Cancer Epidemiol Biomarkers Prev. 1999;8:153–8.PubMedGoogle Scholar
  16. 16.
    Pan D, Narayan D, Ariyan S. Merkel cell carcinoma: five case reports using sentinel lymph node biopsy and a review of 110 new cases. Plast Reconstr Surg. 2002;110:1259–65.PubMedCrossRefGoogle Scholar
  17. 17.
    Karkos PD, Sastry A, Hampal S, Al-Jafari M. Spontaneous regression of Merkel cell carcinoma of the nose. Head Neck. 2010;32:411–4.PubMedGoogle Scholar
  18. 18.
    Kubo H, Matsushita S, Fukushige T, et al. Spontaneous regression of recurrent and metastatic Merkel cell carcinoma. J Dermatol. 2007;34:773–7.PubMedCrossRefGoogle Scholar
  19. 19.
    Wooff JC, Trites, JR, Walsh, NMG, Bullock, MJ: Complete spontaneous regression of metastatic Merkel cell carcinoma: a case report and review of the literature. Am J Dermatopathol. 2010.Google Scholar
  20. 20.
    Ciudad C, Avilés JA, Alfageme F, et al. Spontaneous regression in merkel cell carcinoma: report of two cases with a description of dermoscopic features and review of the literature. Dermatol Surg. 2010;36:687–93.PubMedCrossRefGoogle Scholar
  21. 21.
    •• Feng H, Shuda M, Chang Y, Moore PS. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science. 2008;319:1096–100. The original publication identifying the novel Merkel cell polyomavirus and its association with MCC.PubMedCrossRefGoogle Scholar
  22. 22.
    Garneski KM, Warcola AH, Feng Q, et al. Merkel cell polyomavirus is more frequently present in North American than Australian Merkel cell carcinoma tumors. J Investig Dermatol. 2009;129:246–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Becker JC, Houben R, Ugurel S, et al. MC polyomavirus is frequently present in Merkel cell carcinoma of European patients. J Invest Dermatol. 2009;129:248–50.PubMedCrossRefGoogle Scholar
  24. 24.
    Kassem A, Schöpflin A, Diaz C, et al. Frequent detection of Merkel cell polyomavirus in human Merkel cell carcinomas and identification of a unique deletion in the VP1 gene. Cancer Res. 2008;68:5009–13.PubMedCrossRefGoogle Scholar
  25. 25.
    Katano H, Ito H, Suzuki Y, et al. Detection of Merkel cell polyomavirus in Merkel cell carcinoma and Kaposi’s sarcoma. J Med Virol. 2009;81:1951–8.PubMedCrossRefGoogle Scholar
  26. 26.
    • Houben R, Shuda M, Weinkam R, et al. Merkel cell polyomavirus-infected Merkel cell carcinoma cells require expression of viral T-antigens. J Virol. 2010;84:7064–72. This article reports that MCC cells depend on persistent expression of MCPyV oncoproteins and supports causative role of MCPyV and therapeutic targeting of viral oncoproteins.PubMedCrossRefGoogle Scholar
  27. 27.
    Carter JJ, Paulson KG, Wipf GC, et al. Association of Merkel cell polyomavirus-specific antibodies with Merkel cell carcinoma. J Natl Cancer Inst. 2009;101:1510–22.PubMedCrossRefGoogle Scholar
  28. 28.
    Pulitzer MP, Amin BD, Busam KJ. Merkel cell carcinoma: review. Adv Anat Pathol. 2009;16:135–44.PubMedCrossRefGoogle Scholar
  29. 29.
    Kean JM, Rao S, Wang M, Garcea RL. Seroepidemiology of human polyomaviruses. PLoS Pathog. 2009;5:e1000363.PubMedCrossRefGoogle Scholar
  30. 30.
    Tolstov YL, Pastrana DV, Feng H, et al. Human Merkel cell polyomavirus infection II. MCV is a common human infection that can be detected by conformational capsid epitope immunoassays. Int J Cancer. 2009;125:1250–6.PubMedCrossRefGoogle Scholar
  31. 31.
    Pastrana DV, Tolstov YL, Becker JC, et al. Quantitation of human Seroresponsiveness to Merkel cell polyomavirus. PLoS Pathog. 2009;1:20.Google Scholar
  32. 32.
    Touze A, Le Bidre, E, Laude, H, et al.: High levels of antibodies against Merkel cell polyomavirus identify a subset of patients with Merkel cell carcinoma with better clinical outcome. J Clin Oncol. 2011:1–9Google Scholar
  33. 33.
    Schowalter RM, Pastrana DV, Pumphrey KA, et al. Merkel cell polyomavirus and two previously unknown polyomaviruses are chronically shed from human skin. Cell Host and Microbe. 2011;7:509–15.CrossRefGoogle Scholar
  34. 34.
    Foulongne V, Kluger N, Dereure O, et al. Merkel cell polyomavirus in cutaneous swabs. Emerging Infect Dis. 2010;16:685–7.PubMedGoogle Scholar
  35. 35.
    Wieland U, Silling S, Scola N, et al. Merkel cell polyomavirus infection in HIV-positive men. Arch Dermatol. 2011;147:401–6.PubMedCrossRefGoogle Scholar
  36. 36.
    Dworkin AM, Tseng SY, Allain DC, et al. Merkel cell polyomavirus in cutaneous squamous cell carcinoma of immunocompetent individuals. J Invest Dermatol. 2009;129:2868–74.PubMedCrossRefGoogle Scholar
  37. 37.
    Loyo M, Guerrero-Preston, R, Brait, M, et al.: Quantitative detection of Merkel cell virus in human tissues and possible mode of transmission. Int J Canc. 2010;NA–NA.Google Scholar
  38. 38.
    Kantola K, Sadeghi M, Lahtinen A, et al. Merkel cell polyomavirus DNA in tumor-free tonsillar tissues and upper respiratory tract samples: implications for respiratory transmission and latency. J Clin Virol. 2009;45:292–5.PubMedCrossRefGoogle Scholar
  39. 39.
    Babakir-Mina M, Ciccozzi M, Lo Presti A, et al. Identification of Merkel cell polyomavirus in the lower respiratory tract of Italian patients. J Med Virol. 2010;82:505–9.PubMedCrossRefGoogle Scholar
  40. 40.
    Bialasiewicz S, Lambert SB, Whiley DM, et al. Merkel cell polyomavirus DNA in respiratory specimens from children and adults. Emerg Infect Dis. 2009;15:492–4.PubMedCrossRefGoogle Scholar
  41. 41.
    Goh S, Lindau C, Tiveljung-Lindell A, Allander T. Merkel cell polyomavirus in respiratory tract secretions. Emerg Infect Dis. 2009;15:489–91.PubMedCrossRefGoogle Scholar
  42. 42.
    •• Moore PS, Chang Y. Why do viruses cause cancer? Highlights of the first century of human tumour virology. Nat Rev Canc. 2010;10:878–89. An excellent review of viral carcinogenesis.CrossRefGoogle Scholar
  43. 43.
    Eddy BE, Borman GS, Grubbs GE, Young RD. Identification of the oncogenic substance in rhesus monkey kidney cell culture as simian virus 40. Virology. 1962;17:65–75.PubMedCrossRefGoogle Scholar
  44. 44.
    •• Shuda M, Feng H, Kwun HJ, et al. T-antigen mutations are a human tumor-specific signature for Merkel cell polyomavirus. Proc Natl Acad Sci USA. 2008;105:16272–7. The first of several publications that identified tumor-specific truncating mutations in MCPyV T-antigen DNA PubMedCrossRefGoogle Scholar
  45. 45.
    Ali SH, DeCaprio JA. Cellular transformation by SV40 large T-antigen: interaction with host proteins. Semin Canc Biol. 2001;11:15–23.CrossRefGoogle Scholar
  46. 46.
    Houben R, Adam, C, Baeurle, A, et al.: An intact retinoblastoma protein binding site in merkel cell polyomavirus large T-antigen is required for promoting growth of merkel cell carcinoma cells. Int J Canc Journal international du cancer. 2011.Google Scholar
  47. 47.
    Sihto H, Kukko HM, Koljonen VS, et al. Merkel cell polyomavirus infection, large T-antigen, retinoblastoma protein and outcome in Merkel cell carcinoma. Clin Canc Res. 2011;1:9.Google Scholar
  48. 48.
    Bhatia K, Goedert JJ, Modali R, et al. Merkel cell carcinoma subgroups by Merkel cell polyomavirus DNA relative abundance and oncogene expression. Int J Canc Journal international du cancer. 2010;126:2240–6.Google Scholar
  49. 49.
    Segawa K, Minowa A, Sugasawa K, et al. Abrogation of p53-mediated transactivation by SV40 large T-antigen. Oncogene. 1993;8:543–8.PubMedGoogle Scholar
  50. 50.
    Jiang D, Srinivasan A, Lozano G, Robbins PD. SV40 T-antigen abrogates p53-mediated transcriptional activity. Oncogene. 1993;8:2805–12.PubMedGoogle Scholar
  51. 51.
    Oren M, Maltzman W, Levine AJ. Post-translational regulation of the 54 K cellular tumor antigen in normal and transformed cells. Mol Cell Biol. 1981;1:101–10.PubMedGoogle Scholar
  52. 52.
    Pipas JM, Levine AJ. Role of T-antigen interactions with p53 in tumorigenesis. Semin Canc Biol. 2001;11:23–30.CrossRefGoogle Scholar
  53. 53.
    Ahuja D, Sáenz-Robles MT, Pipas JM. SV40 large T-antigen targets multiple cellular pathways to elicit cellular transformation. Oncogene. 2005;24:7729–45.PubMedCrossRefGoogle Scholar
  54. 54.
    Schmid M, Janssen K, Dockhorn-Dworniczak B, et al. p53 abnormalities are rare events in neuroendocrine (Merkel cell) carcinoma of the skin. An immunohistochemical and SSCP analysis. Virchows Arch. 1997;430:233–7.PubMedCrossRefGoogle Scholar
  55. 55.
    Van Gele M, Kaghad M, Leonard JH, et al. Mutation analysis of P73 and TP53 in Merkel cell carcinoma. Br J Canc. 2000;82:823–6.CrossRefGoogle Scholar
  56. 56.
    Bhatia K, Goedert, JJ, Modali, R, et al.: Immunological detection of viral large T-antigen identifies a subset of merkel cell carcinoma tumors with higher viral abundance and better clinical outcome. Int J Canc Journal international du cancer. 2009.Google Scholar
  57. 57.
    Waltari M, Sihto, H, Kukko, H, et al.: Association of Merkel cell polyomavirus infection with tumor p53, KIT, stem cell factor, PDGFR-alpha and survival in Merkel cell carcinoma. Int J Canc Journal international du cancer. 2010.Google Scholar
  58. 58.
    Shuda M, Arora R, Kwun HJ, et al. Human Merkel cell polyomavirus infection I. MCV T-antigen expression in Merkel cell carcinoma, lymphoid tissues and lymphoid tumors. Int J Canc. 2009;125:1243–9.CrossRefGoogle Scholar
  59. 59.
    Faust H, Pastrana DV, Buck CB, et al. Antibodies to Merkel cell polyomavirus correlate to presence of viral DNA in the skin. J Infect Dis. 2011;203:1096–100.PubMedCrossRefGoogle Scholar
  60. 60.
    • Paulson KG, Carter, JJ, Johnson, LG, et al.: Antibodies to Merkel cell polyomavirus T-antigen oncoproteins reflect tumor burden in Merkel cell carcinoma patients. Canc Res. 2010. This report identifies a potential biomarker to track MCC burden and predict relapse prior to conventional clinical approaches. Google Scholar
  61. 61.
    Nakamura T, Sato Y, Watanabe D, et al. Nuclear localization of Merkel cell polyomavirus large T-antigen in Merkel cell carcinoma. Virology. 2010;398:273–9.PubMedCrossRefGoogle Scholar
  62. 62.
    Andea AA, Coit DG, Amin B, Busam KJ. Merkel cell carcinoma: histologic features and prognosis. Cancer. 2008;113:2549–58.PubMedCrossRefGoogle Scholar
  63. 63.
    • Paulson KG, Iyer, JG, Tegeder, AR, et al.: Transcriptome-wide studies of Merkel cell carcinoma and validation of intratumoral CD8+ lymphocyte invasion as an independent predictor of survival. J Clin Oncol. 2011. This report underscores the importance of immune cell infiltration in MCC tumors and its association with improved prognosis, hence supporting the use of immunotherapy in MCC. Google Scholar
  64. 64.
    •• Dunn GP, Bruce AT, Ikeda H, et al. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol. 2002;3:991–8. This is an excellent summary of key steps in tumor immune evasion.PubMedCrossRefGoogle Scholar
  65. 65.
    Hansen TH, Bouvier M. MHC class I antigen presentation: learning from viral evasion strategies. Nat Rev Immunol. 2009;9:503–13.PubMedCrossRefGoogle Scholar
  66. 66.
    Haque M, Ueda K, Nakano K, et al. Major histocompatibility complex class I molecules are down-regulated at the cell surface by the K5 protein encoded by Kaposi’s sarcoma-associated herpesvirus/human herpesvirus-8. J Gen Virol. 2001;82:1175–80.PubMedGoogle Scholar
  67. 67.
    Hayashi H, Tanaka K, Jay F, et al. Modulation of the tumorigenicity of human adenovirus-12-transformed cells by interferon. Cell. 1985;43:263–7.PubMedCrossRefGoogle Scholar
  68. 68.
    Hill A, Jugovic P, York I, et al. Herpes simplex virus turns off the TAP to evade host immunity. Nature. 1995;375:411–5.PubMedCrossRefGoogle Scholar
  69. 69.
    Koopman LA, van Der Slik AR, Giphart MJ, Fleuren GJ. Human leukocyte antigen class I gene mutations in cervical cancer. J Natl Canc Inst. 1999;91:1669–77.CrossRefGoogle Scholar
  70. 70.
    Cromme FV, van Bommel PF, Walboomers JM, et al. Differences in MHC and TAP-1 expression in cervical cancer lymph node metastases as compared with the primary tumours. Br J Canc. 1994;69:1176–81.CrossRefGoogle Scholar
  71. 71.
    Seliger B, Maeurer MJ, Ferrone S. TAP off–tumors on. Immunol Today. 1997;18:292–9.PubMedCrossRefGoogle Scholar
  72. 72.
    Takaoka A, Hayakawa S, Yanai H, et al. Integration of interferon-alpha/beta signalling to p53 responses in tumour suppression and antiviral defence. Nature. 2003;424:516–23.PubMedCrossRefGoogle Scholar
  73. 73.
    Chin YE, Kitagawa M, Su WC, et al. Cell growth arrest and induction of cyclin-dependent kinase inhibitor p21 WAF1/CIP1 mediated by STAT1. Science. 1996;272:719–22.PubMedCrossRefGoogle Scholar
  74. 74.
    Goronzy JJ, Lee W-W, Weyand CM. Aging and T-cell diversity. Exp Gerontol. 2007;42:400–6.PubMedCrossRefGoogle Scholar
  75. 75.
    Mogha A, Fautrel A, Mouchet N, et al. Merkel cell polyomavirus small T-antigen mRNA level is increased following in vivo UV-radiation. PLoS ONE. 2010;5:e11423.PubMedCrossRefGoogle Scholar
  76. 76.
    Ullrich SE. Mechanisms underlying UV-induced immune suppression. Mutat Res. 2005;571:185–205.PubMedCrossRefGoogle Scholar
  77. 77.
    Granstein RD, Matsui MS. UV radiation-induced immunosuppression and skin cancer. Cutis; cutaneous medicine for the practitioner. 2004;74:4–9.PubMedGoogle Scholar
  78. 78.
    Halliday GM, Bestak R, Yuen KS, et al. UVA-induced immunosuppression. Mutat Res. 1998;422:139–45.PubMedCrossRefGoogle Scholar
  79. 79.
    Teicher BA. Transforming growth factor-beta and the immune response to malignant disease. Clin Canc Res. 2007;13:6247–51.CrossRefGoogle Scholar
  80. 80.
    Houston A, Bennett MW, O’Sullivan GC, et al. Fas ligand mediates immune privilege and not inflammation in human colon cancer, irrespective of TGF-beta expression. Br J Canc. 2003;89:1345–51.CrossRefGoogle Scholar
  81. 81.
    Khong HT, Restifo NP. Natural selection of tumor variants in the generation of “tumor escape” phenotypes. Nat Immunol. 2002;3:999–1005.PubMedCrossRefGoogle Scholar
  82. 82.
    Rubinstein N, Ilarregui JM, Toscano MA, Rabinovich GA. The role of galectins in the initiation, amplification and resolution of the inflammatory response. Tissue Antigens. 2004;64:1–12.PubMedCrossRefGoogle Scholar
  83. 83.
    Uyttenhove C, Pilotte L, Théate I, et al. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat Med. 2003;9:1269–74.PubMedCrossRefGoogle Scholar
  84. 84.
    Wang T, Niu G, Kortylewski M, et al. Regulation of the innate and adaptive immune responses by Stat-3 signaling in tumor cells. Nat Med. 2004;10:48–54.PubMedCrossRefGoogle Scholar
  85. 85.
    Groh V, Rhinehart R, Randolph-Habecker J, et al. Costimulation of CD8alphabeta T cells by NKG2D via engagement by MIC induced on virus-infected cells. Nat Immunol. 2001;2:255–60.PubMedCrossRefGoogle Scholar
  86. 86.
    Terabe M, Berzofsky JA. Immunoregulatory T cells in tumor immunity. Curr Opin Immunol. 2004;16:157–62.PubMedCrossRefGoogle Scholar
  87. 87.
    Zou W. Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol. 2006;6:295–307.PubMedCrossRefGoogle Scholar
  88. 88.
    Kusmartsev S, Nagaraj S, Gabrilovich DI. Tumor-associated CD8+ T cell tolerance induced by bone marrow-derived immature myeloid cells. J Immunol. 2005;175:4583–92.PubMedGoogle Scholar
  89. 89.
    Zajac AJ, Blattman JN, Murali-Krishna K, et al. Viral immune evasion due to persistence of activated T cells without effector function. J Exp Med. 1998;188:2205–13.PubMedCrossRefGoogle Scholar
  90. 90.
    Gallimore A, Glithero A, Godkin A, et al. Induction and exhaustion of lymphocytic choriomeningitis virus-specific cytotoxic T lymphocytes visualized using soluble tetrameric major histocompatibility complex class I-peptide complexes. J Exp Med. 1998;187:1383–93.PubMedCrossRefGoogle Scholar
  91. 91.
    Wherry EJ, Blattman JN, Murali-Krishna K, et al. Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment. J Virol. 2003;77:4911–27.PubMedCrossRefGoogle Scholar
  92. 92.
    Barber DL, Wherry EJ, Masopust D, et al. Restoring function in exhausted CD8 T cells during chronic viral infection. Nature. 2006;439:682–7.PubMedCrossRefGoogle Scholar
  93. 93.
    Kim J, Mcniff JM. Nuclear expression of survivin portends a poor prognosis in Merkel cell carcinoma. Mod Pathol. 2008;21:764–9.PubMedCrossRefGoogle Scholar
  94. 94.
    Ames HM, Bichakjian CK, Liu GY, et al. Huntingtin-interacting protein 1: a Merkel cell carcinoma marker that interacts with c-Kit. J Invest Dermatol. 2011;1:8.Google Scholar
  95. 95.
    Curran MA, Kim M, Montalvo W, et al. Combination CTLA-4 blockade and 4-1BB activation enhances tumor rejection by increasing T-cell infiltration, proliferation, and cytokine production. PLoS ONE. 2011;6:e19499.PubMedCrossRefGoogle Scholar
  96. 96.
    Palazon A, Teijeira A, Martinez-Forero I, et al. Agonist anti-CD137 mAb act on tumor endothelial cells to enhance recruitment of activated T lymphocytes. Canc Res. 2011;71:801–11.CrossRefGoogle Scholar
  97. 97.
    Iyer JG, Afanasiev OK, McClurkan C, et al. Merkel cell polyomavirus-specific CD8+ and CD4+ T-cell responses identified in Merkel cell carcinomas and blood. Clin Cancer Res. 2011; doi:10.1158/1078-0432.CCR-11-1513.
  98. 98.
    Shuda M, Kwun HJ, Feng H, et al. Human Merkel cell polyomavirus small T antigen is an oncoprotein targeting the 4E-BP1 translation regulator. J Clin Investig. 2011; doi:10.1172/JCI46323.

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Shailender Bhatia
    • 1
  • Olga Afanasiev
    • 2
  • Paul Nghiem
    • 3
  1. 1.Departments of Medicine/Medical OncologyUniversity of Washington, Fred Hutchinson Cancer Research Center, Seattle Cancer Care AllianceSeattleUSA
  2. 2.Departments of Medicine/Dermatology, PathologyUniversity of WashingtonSeattleUSA
  3. 3.Departments of Medicine/Dermatology, PathologyUniversity of Washington, Fred Hutchinson Cancer Research Center, Seattle Cancer Care AllianceSeattleUSA

Personalised recommendations