Advanced search
Publication Cover
Expert Review of Molecular Diagnostics Volume 16, 2016 - Issue 2
Submit an article Journal homepage
536
Views
20
CrossRef citations to date
0
Altmetric
Reviews

Prognostic and predictive biomarkers in melanoma: an update

Mona FothOncoMark Ltd., NovaUCD, Bellfield, University College Dublin, Dublin, Ireland;Cancer Research UK, Beatson Institute, Glasgow, United Kingdom
,
Jasper WoutersOncoMark Ltd., NovaUCD, Bellfield, University College Dublin, Dublin, Ireland;Translational Cell & Tissue Research, Department of Imaging and Pathology, Katholieke Universiteit Leuven, Leuven, Belgium
,
Ciaran de ChaumontOncoMark Ltd., NovaUCD, Bellfield, University College Dublin, Dublin, Ireland;Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland
,
Peter DynoodtOncoMark Ltd., NovaUCD, Bellfield, University College Dublin, Dublin, IrelandCorrespondence[email protected] [email protected]
&
William M. GallagherOncoMark Ltd., NovaUCD, Bellfield, University College Dublin, Dublin, Ireland;UCD Cancer Biology and Therapeutics Laboratory, School of Biomolecular and Biomedical Science, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland
Pages 223-237 | Received 06 Aug 2015, Accepted 27 Nov 2015, Published online: 22 Dec 2015

References

  • Papers of special note have been highlighted as:
  • • of interest
  • •• of considerable interest
  • Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011;364(26):2517–2526.
  • Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364(26):2507–2516.
  • Hodis E, Watson IR, Kryukov GV, et al. A landscape of driver mutations in melanoma. Cell. 2012;150(2):251–263.
  • Shtivelman E, Davies MQ, Hwu P, et al. Pathways and therapeutic targets in melanoma. Oncotarget. 2014;5(7):1701–1752.
  • Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417(6892):949–954.
  • van den Hurk K, Balint B, Toomey S, et al. High-throughput oncogene mutation profiling shows demographic differences in BRAF mutation rates among melanoma patients. Melanoma Res. 2015;25(3):189–199.
  • Rubinstein JC, Sznol M, Pavlick AC, et al. Incidence of the V600K mutation among melanoma patients with BRAF mutations, and potential therapeutic response to the specific BRAF inhibitor PLX4032. J Transl Med. 2010;8:67.
  • Maurer G, Tarkowski B, Baccarini M. Raf kinases in cancer-roles and therapeutic opportunities. Oncogene. 2011;30(32):3477–3488.
  • Yeh I, Von Deimling A, Bastian BC. Clonal BRAF mutations in melanocytic nevi and initiating role of BRAF in melanocytic neoplasia. J Natl Cancer Inst. 2013;105(12):917–919.
  • Pollock PM, Harper UL, Hansen KS, et al. High frequency of BRAF mutations in nevi. Nat Genet. 2003;33(1):19–20.
  • Akslen LA, Angelini S, Straume O, et al. BRAF and NRAS mutations are frequent in nodular melanoma but are not associated with tumor cell proliferation or patient survival. J Invest Dermatol. 2005;125(2):312–317.
  • Long GV, Menzies AM, Nagrial AM, et al. Prognostic and clinicopathologic associations of oncogenic BRAF in metastatic melanoma. J Clin Oncol. 2011;29(10):1239–1246.
  • Cheng Y, Lu J, Chen G, et al. Stage-specific prognostic biomarkers in melanoma. Oncotarget. 2015;6(6):4180–4189.
  • Safaee Ardekani G, Jafarnejad SM, Khosravi S, et al. Disease progression and patient survival are significantly influenced by BRAF protein expression in primary melanoma. Br J Dermatol. 2013;169(2):320–328.
  • Edlundh-Rose E, Egyhazi S, Omholt K, et al. NRAS and BRAF mutations in melanoma tumours in relation to clinical characteristics: a study based on mutation screening by pyrosequencing. Melanoma Res. 2006;16(6):471–478.
  • Goel VK, Lazar AJ, Warneke CL, et al. Examination of mutations in BRAF, NRAS, and PTEN in primary cutaneous melanoma. J Invest Dermatol. 2006;126(1):154–160.
  • Ekedahl H, Cirenajwis H, Harbst K, et al. The clinical significance of BRAF and NRAS mutations in a clinic-based metastatic melanoma cohort. Br J Dermatol. 2013;169(5):1049–1055.
  • Smalley KS. Understanding melanoma signaling networks as the basis for molecular targeted therapy. J Invest Dermatol. 2010;130(1):28–37.
  • Omholt K, Platz A, Kanter L, et al. NRAS and BRAF mutations arise early during melanoma pathogenesis and are preserved throughout tumor progression. Clin Cancer Res. 2003;9(17):6483–6488.
  • Platz A, Egyhazi S, Ringborg U, et al. Human cutaneous melanoma; a review of NRAS and BRAF mutation frequencies in relation to histogenetic subclass and body site. Mol Oncol. 2008;1(4):395–405.
  • Slipicevic A, Herlyn M. KIT in melanoma: many shades of gray. J Invest Dermatol. 2015;135(2):337–338.
  • Van Raamsdonk CD, Bezrookove V, Green G, et al. Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi. Nature. 2009;457(7229):599–602.
  • Van Raamsdonk CD, Griewank KG, Crosby MB, et al. Mutations in GNA11 in uveal melanoma. N Engl J Med. 2010;363(23):2191–2199.
  • Krauthammer M, Kong Y, Ha BH, et al. Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma. Nat Genet. 2012;44(9):1006–1014.
  • Li A, Ma Y, Jin M, et al. Activated mutant NRas(Q61K) drives aberrant melanocyte signaling, survival, and invasiveness via a Rac1-dependent mechanism. J Invest Dermatol. 2012;132(11):2610–2621.
  • Li A, Machesky LM. Melanoblasts on the move: Rac1 sets the pace. Small GTPases. 2012;3(2):115–119.
  • Berger MF, Hodis E, Heffernan TP, et al. Melanoma genome sequencing reveals frequent PREX2 mutations. Nature. 2012;485(7399):502–506.
  • Maertens O, Johnson B, Hollstein P, et al. Elucidating distinct roles for NF1 in melanomagenesis. Cancer Discov. 2013;3(3):338–349.
  • Huang FW, Hodis E, Xu MJ, et al. Highly recurrent TERT promoter mutations in human melanoma. Science. 2013;339(6122):957–959.
  • Aguissa-Toure AH, Li G. Genetic alterations of PTEN in human melanoma. Cell Mol Life Sci. 2012;69(9):1475–1491.
  • Hurlstone A, Wellbrock C. TP53 in the UV spotlight: a bona fide driver of melanoma. Pigment Cell Melanoma Res. 2014;27(6):1010–1011.
  • Hocker T, Tsao H. Ultraviolet radiation and melanoma: a systematic review and analysis of reported sequence variants. Hum Mutat. 2007;28(6):578–588.
  • Gembarska A, Luciani F, Fedele C, et al. MDM4 is a key therapeutic target in cutaneous melanoma. Nat Med. 2012;18(8):1239–1247.
  • Hussussian CJ, Struewing JP, Goldstein AM, et al. Germline p16 mutations in familial melanoma. Nat Genet. 1994;8(1):15–21.
  • Goldstein AM, Chan M, Harland M, et al. Features associated with germline CDKN2A mutations: a GenoMEL study of melanoma-prone families from three continents. J Med Genet. 2007;44(2):99–106.
  • Sosman JA, Kim KB, Schuchter L, et al. Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N Engl J Med. 2012;366(8):707–714.
  • Hauschild A, Grob JJ, Demidov LV, et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2012;380(9839):358–365.
  • Flaherty KT, Robert C, Hersey P, et al. Improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl J Med. 2012;367(2):107–114.
  • Guo J, Si L, Kong Y, et al. Phase II, open-label, single-arm trial of imatinib mesylate in patients with metastatic melanoma harboring c-Kit mutation or amplification. J Clin Oncol. 2011;29(21):2904–2909.
  • Flaherty KT, Infante JR, Daud A, et al. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N Engl J Med. 2012;367(18):1694–1703.
  • Kirkwood JM, Ibrahim JG, Sondak VK, et al. High- and low-dose interferon alfa-2b in high-risk melanoma: first analysis of intergroup trial E1690/S9111/C9190. J Clin Oncol. 2000;18(12):2444–2458.
  • Eggermont AM, Suciu S, Santinami M, et al. Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: final results of EORTC 18991, a randomised phase III trial. Lancet. 2008;372(9633):117–126.
  • Atkins MB, Lotze MT, Dutcher JP, et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol. 1999;17(7):2105–2116.
  • Atkins MB, Kunkel L, Sznol M, et al. High-dose recombinant interleukin-2 therapy in patients with metastatic melanoma: long-term survival update. Cancer J Sci Am. 2000;6(Suppl 1):S11–S14.
  • Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–723.
  • Wang W, Yu D, Sarnaik AA, et al. Biomarkers on melanoma patient T cells associated with ipilimumab treatment. J Transl Med. 2012;10(146):1479–5876.
  • Yuan J, Adamow M, Ginsberg BA, et al. Integrated NY-ESO-1 antibody and CD8+ T-cell responses correlate with clinical benefit in advanced melanoma patients treated with ipilimumab. Proc Natl Acad Sci U S A. 2011;108(40):16723–16728.
  • Fu T, He Q, Sharma P. The ICOS/ICOSL pathway is required for optimal antitumor responses mediated by anti-CTLA-4 therapy. Cancer Res. 2011;71(16):5445–5454.
  • Robert C, Ribas A, Wolchok JD, et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet. 2014;384(9948):1109–1117.
  • Robert C, Schachter J, Long GV, et al. Pembrolizumab versus Ipilimumab in Advanced Melanoma. N Engl J Med. 2015;372(26):2521–2532.
  • Robert C, Long GV, Brady B, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372(4):320–330.
  • Herbst RS, Soria JC, Kowanetz M, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014;515(7528):563–567.

•• Evaluates the safety, activity and biomarkers of programmed death ligand-1 inhibition using an engineered humanized antibody.

  • Brahmer JR, Tykodi SS, Chow LQ, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012;366(26):2455–2465.
  • Hu-Lieskovan S, Robert L, Homet Moreno B, et al. Combining targeted therapy with immunotherapy in BRAF-mutant melanoma: promise and challenges. J Clin Oncol. 2014;32(21):2248–2254.
  • Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med. 2015;373(13):1270–1271.
  • Svane IM, Verdegaal EM. Achievements and challenges of adoptive T cell therapy with tumor-infiltrating or blood-derived lymphocytes for metastatic melanoma: what is needed to achieve standard of care? Cancer Immunol Immunother. 2014;63(10):1081–1091.
  • Radvanyi LG, Bernatchez C, Zhang M, et al. Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients. Clin Cancer Res. 2012;18(24):6758–6770.
  • Rosenberg SA, Yang JC, Sherry RM, et al. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin Cancer Res. 2011;17(13):4550–4557.
  • Cafri G, Sharbi-Yunger A, Tzehoval E, et al. mRNA-transfected dendritic cells expressing polypeptides which link MHC-I presentation to constitutive TLR4 activation confer tumor immunity. Mol Ther. 2015;23(8):1391–1400.
  • Wilgenhof S, Corthals J, Van Nuffel AM, et al. Long-term clinical outcome of melanoma patients treated with messenger RNA-electroporated dendritic cell therapy following complete resection of metastases. Cancer Immunol Immunother. 2015;64(3):381–388.
  • Weinstein D, Leininger J, Hamby C, et al. Diagnostic and prognostic biomarkers in melanoma. J Clin Aesthet Dermatol. 2014;7(6):13–24.
  • Altman DG, McShane LM, Sauerbrei W, et al. Reporting recommendations for tumor marker prognostic studies (REMARK): explanation and elaboration. BMC Med. 2012;10(51):1741–7015.

•• Provides a comprehensive overview to educate on good reporting and provide a valuable reference of issues to consider when designing, conducting and analyzing tumor marker studies and prognostic studies in medicine in general.

  • Mandala M, Massi D. Tissue prognostic biomarkers in primary cutaneous melanoma. Virchows Arch. 2014;464(3):265–281.
  • Gerami P, Jewell SS, Pouryazdanparast P, et al. Copy number gains in 11q13 and 8q24 [corrected] are highly linked to prognosis in cutaneous malignant melanoma. J Mol Diagn. 2011;13(3):352–358.
  • Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–674.
  • Gammon B, Beilfuss B, Guitart J, et al. Enhanced detection of spitzoid melanomas using fluorescence in situ hybridization with 9p21 as an adjunctive probe. Am J Surg Pathol. 2012;36(1):81–88.
  • Gerami P, Sorrell J, Martini M. Dermatoscopic evolution of dysplastic nevi showing high-grade dysplasia in a metastatic melanoma patient on vemurafenib. J Am Acad Dermatol. 2012;67(6):e275–276.
  • Gerami P, Scolyer RA, Xu X, et al. Risk assessment for atypical spitzoid melanocytic neoplasms using FISH to identify chromosomal copy number aberrations. Am J Surg Pathol. 2013;37(5):676–684.
  • Gerami P, Li G, Pouryazdanparast P, et al. A highly specific and discriminatory FISH assay for distinguishing between benign and malignant melanocytic neoplasms. Am J Surg Pathol. 2012;36(6):808–817.
  • Pouryazdanparast P, Cowen DP, Beilfuss BA, et al. Distinctive clinical and histologic features in cutaneous melanoma with copy number gains in 8q24. Am J Surg Pathol. 2012;36(2):253–264.
  • Gammon B, Ali L, Guitart J, et al. Homogeneous staining regions for cyclin D1, a marker of poor prognosis in malignant melanoma. Am J Dermatopathol. 2012;34(5):487–490.
  • Vergier B, Prochazkova-Carlotti M, de la Fouchardiere A, et al. Fluorescence in situ hybridization, a diagnostic aid in ambiguous melanocytic tumors: European study of 113 cases. Mod Pathol. 2011;24(5):613–623.
  • Massi D, Cesinaro AM, Tomasini C, et al. Atypical Spitzoid melanocytic tumors: a morphological, mutational, and FISH analysis. J Am Acad Dermatol. 2011;64(5):919–935.
  • Gaiser T, Kutzner H, Palmedo G, et al. Classifying ambiguous melanocytic lesions with FISH and correlation with clinical long-term follow up. Mod Pathol. 2010;23(3):413–419.
  • Raskin L, Ludgate M, Iyer RK, et al. Copy number variations and clinical outcome in atypical spitz tumors. Am J Surg Pathol. 2011;35(2):243–252.
  • Winnepenninckx V, Lazar V, Michiels S, et al. Gene expression profiling of primary cutaneous melanoma and clinical outcome. J Natl Cancer Inst. 2006;98(7):472–482.
  • Mandruzzato S, Callegaro A, Turcatel G, et al. A gene expression signature associated with survival in metastatic melanoma. J Transl Med. 2006;4:50.
  • Alonso SR, Tracey L, Ortiz P, et al. A high-throughput study in melanoma identifies epithelial-mesenchymal transition as a major determinant of metastasis. Cancer Res. 2007;67(7):3450–3460.
  • Kashani-Sabet M, Venna S, Nosrati M, et al. A multimarker prognostic assay for primary cutaneous melanoma. Clin Cancer Res. 2009;15(22):6987–6992.
  • Gould Rothberg BE, Berger AJ, Molinaro AM, et al. Melanoma prognostic model using tissue microarrays and genetic algorithms. J Clin Oncol. 2009;27(34):5772–5780.
  • Jonsson G, Busch C, Knappskog S, et al. Gene expression profiling-based identification of molecular subtypes in stage IV melanomas with different clinical outcome. Clin Cancer Res. 2010;16(13):3356–3367.
  • Bogunovic D, O’Neill DW, Belitskaya-Levy I, et al. Immune profile and mitotic index of metastatic melanoma lesions enhance clinical staging in predicting patient survival. Proc Natl Acad Sci U S A. 2009;106(48):20429–20434.
  • Sivendran S, Chang R, Pham L, et al. Dissection of immune gene networks in primary melanoma tumors critical for antitumor surveillance of patients with stage II-III resectable disease. J Invest Dermatol. 2014;134(8):2202–2211.
  • Caramuta S, Egyhazi S, Rodolfo M, et al. MicroRNA expression profiles associated with mutational status and survival in malignant melanoma. J Invest Dermatol. 2010;130(8):2062–2070.
  • Friedman EB, Shang S, de Miera EV, et al. Serum microRNAs as biomarkers for recurrence in melanoma. J Transl Med. 2012;10:155.
  • Pencheva N, Tran H, Buss C, et al. Convergent multi-miRNA targeting of ApoE drives LRP1/LRP8-dependent melanoma metastasis and angiogenesis. Cell. 2012;151(5):1068–1082.
  • Haqq C, Nosrati M, Sudilovsky D, et al. The gene expression signatures of melanoma progression. Proc Natl Acad Sci U S A. 2005;102(17):6092–6097.
  • Camp RL, Chung GG, Rimm DL. Automated subcellular localization and quantification of protein expression in tissue microarrays. Nat Med. 2002;8(11):1323–1327.
  • Timar J, Gyorffy B, Raso E. Gene signature of the metastatic potential of cutaneous melanoma: too much for too little? Clin Exp Metastasis. 2010;27(6):371–387.
  • John T, Black MA, Toro TT, et al. Predicting clinical outcome through molecular profiling in stage III melanoma. Clin Cancer Res. 2008;14(16):5173–5180.
  • Bittner M, Meltzer P, Chen Y, et al. Molecular classification of cutaneous malignant melanoma by gene expression profiling. Nature. 2000;406(6795):536–540.
  • Schramm SJ, Campain AE, Scolyer RA, et al. Review and cross-validation of gene expression signatures and melanoma prognosis. J Invest Dermatol. 2012;132(2):274–283.

• Demonstrates significant overrepresentation of gene signatures containing immune response processes and the G-protein signaling NRAS-regulation pathway when investigating prognostic signatures from five studies.

  • Mann GJ, Pupo GM, Campain AE, et al. BRAF mutation, NRAS mutation, and the absence of an immune-related expressed gene profile predict poor outcome in patients with stage III melanoma. J Invest Dermatol. 2013;133(2):509–517.
  • Segura MF, Greenwald HS, Hanniford D, et al. MicroRNA and cutaneous melanoma: from discovery to prognosis and therapy. Carcinogenesis. 2012;33(10):1823–1832.
  • Cancer Genome Atlas Network. Electronic address imo, Cancer Genome Atlas N. Genomic Classification of Cutaneous Melanoma. Cell. 2015;161(7):1681–1696.

•• Description of the landscape of genomic alterations in cutaneous melanomas through DNA, RNA and protein-based analysis.

• Describes the treatment of metastatic melanoma with PLX4032 in patients that carry the V600E BRAF mutation resulted in complete or partial regression in the majority of patients.

  • Gallagher SJ, Thompson JF, Indsto J, et al. p16INK4a expression and absence of activated B-RAF are independent predictors of chemosensitivity in melanoma tumors. Neoplasia. 2008;10(11):1231–1239.
  • Linardou H, Pentheroudakis G, Varthalitis I, et al. Predictive biomarkers to chemotherapy in patients with advanced melanoma receiving the combination of cisplatin–vinblastine–temozolomide (PVT) as first-line treatment: a study of the Hellenic Cooperative Oncology Group (HECOG). Anticancer Res. 2015;35(2):1105–1113.
  • Ugurel S, Hildenbrand R, Zimpfer A, et al. Lack of clinical efficacy of imatinib in metastatic melanoma. Br J Cancer. 2005;92(8):1398–1405.
  • Hodi FS, Friedlander P, Corless CL, et al. Major response to imatinib mesylate in KIT-mutated melanoma. J Clin Oncol. 2008;26(12):2046–2051.
  • Snyder A, Makarov V, Merghoub T, et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med. 2014;371(23):2189–2199.

• Describes the findings that define the genetic basis for benefit from cytotoxic T-lymphocyte antigen 4 (CTLA-4) blockade in melanoma and provides a rationale for examining exomes of patients for whom anti-CTLA-4 agents are being considered.

  • Tumeh PC, Harview CL, Yearley JH, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014;515(7528):568–571.
  • Madore J, Vilain RE, Menzies AM, et al. PD-L1 expression in melanoma shows marked heterogeneity within and between patients: implications for anti-PD-1/PD-L1 clinical trials. Pigment Cell Melanoma Res. 2015;28(3):245–253.
  • Bedikian AY, Millward M, Pehamberger H, et al. Bcl-2 antisense (oblimersen sodium) plus dacarbazine in patients with advanced melanoma: the Oblimersen Melanoma Study Group. J Clin Oncol. 2006;24(29):4738–4745.
  • Soengas MS, Lowe SW. Apoptosis and melanoma chemoresistance. Oncogene. 2003;22(20):3138–3151.
  • Gogas H, Ioannovich J, Dafni U, et al. Prognostic significance of autoimmunity during treatment of melanoma with interferon. N Engl J Med. 2006;354(7):709–718.
  • Khoja L, Shenjere P, Hodgson C, et al. Prevalence and heterogeneity of circulating tumour cells in metastatic cutaneous melanoma. Melanoma Res. 2014;24(1):40–46.
  • De Giorgi V, Pinzani P, Salvianti F, et al. Application of a filtration- and isolation-by-size technique for the detection of circulating tumor cells in cutaneous melanoma. J Invest Dermatol. 2010;130(10):2440–2447.
  • Khoja L, Lorigan P, Zhou C, et al. Biomarker utility of circulating tumor cells in metastatic cutaneous melanoma. J Invest Dermatol. 2013;133(6):1582–1590.
  • Reid AL, Millward M, Pearce R, et al. Markers of circulating tumour cells in the peripheral blood of patients with melanoma correlate with disease recurrence and progression. Br J Dermatol. 2013;168(1):85–92.
  • Gajewski TF. Molecular profiling of melanoma and the evolution of patient-specific therapy. Semin Oncol. 2011;38(2):236–242.
  • De Vries IJ, Bernsen MR, Lesterhuis WJ, et al. Immunomonitoring tumor-specific T cells in delayed-type hypersensitivity skin biopsies after dendritic cell vaccination correlates with clinical outcome. J Clin Oncol. 2005;23(24):5779–5787.
  • Lopez MN, Pereda C, Segal G, et al. Prolonged survival of dendritic cell-vaccinated melanoma patients correlates with tumor-specific delayed type IV hypersensitivity response and reduction of tumor growth factor beta-expressing T cells. J Clin Oncol. 2009;27(6):945–952.
  • Ulloa-Montoya F, Louahed J, Dizier B, et al. Predictive gene signature in MAGE-A3 antigen-specific cancer immunotherapy. J Clin Oncol. 2013;31(19):2388–2395.
  • Ji RR, Chasalow SD, Wang L, et al. An immune-active tumor microenvironment favors clinical response to ipilimumab. Cancer Immunol Immunother. 2012;61(7):1019–1031.
  • Collins FS, Hamburg MA. First FDA authorization for next-generation sequencer. N Engl J Med. 2013;369(25):2369–2371.
  • Joyce CW, Murphy IG, Rafferty M, et al. Tumor profiling using protein biomarker panels in malignant melanoma: application of tissue microarrays and beyond. Expert Rev Proteomics. 2012;9(4):415–423.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.