Current status and perspectives in immunotherapy for metastatic melanoma

Riccardo Marconcini ¹, Francesco Spagnolo ², Luigia Stefania Stucci ³, Simone Ribero ⁴, Elena Marra ⁴, Francesco De Rosa ⁵, Virginia Picasso ², Lorenza Di Guardo ⁶, Carolina Cimminiello ⁶, Stefano Cavalieri ⁶, Laura Orgiano ⁷, Enrica Tanda ², Laura Spano ², Alfredo Falcone ¹, Paola Queirolo ², Italian Melanoma Intergroup (IMI)

Affiliations

¹ Unit of Medical Oncology 2, Azienda Ospedaliera-Universitaria Pisana, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Italy.
² Department of Medical Oncology, IRCCS AOU San Martino-Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
³ Medical Oncology Unit, Department of Biomedical Sciences and Clinical Oncology, University of Bari, Bari, Italy.
⁴ Dermatologic Clinic, Department of Medical Sciences, University of Turin, Turin, Italy.
⁵ Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, IRST IRCCS, Meldola, Italy.
⁶ Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
⁷ AOU Cagliari, Department of Medical Oncology, University of Cagliari, Cagliari, Italy.

PMID: 29552325
113 References
24 citations

Abstract

Metastatic melanoma was the first malignancy in which immune checkpoint inhibitors demonstrated their successful efficacy. Currently, the knowledge on the interaction between the immune system and malignant disease is steadily increasing and new drugs and therapeutic strategies are overlooking in the clinical scenario. To provide a comprehensive overview of immune modulating drugs currently available in the treatment of melanoma as well as to discuss of possible future strategies in the metastatic melanoma setting, the present review aims at analyzing controversial aspects about the optimal immunomodulating treatment sequences, the search for biomarkers of efficacy of immunocheckpoint inhibitors, and innovative combinations of drugs currently under investigation.

Keywords: immunotherapy; ipilimumab; melanoma; nivolumab; pembrolizumab.

Other Links

Free PMC article
Full text on Oncotarget

References
Cited By

References
Combined low-dose ipilimumab and pembrolizumab after sequential ipilimumab and pembrolizumab failure in advanced melanoma. Michael C Kirchberger, Axel Hauschild, Gerold Schuler, Lucie Heinzerling. Eur J Cancer, 2016 Aug 09; 65. PMID: 27501507
Sequential administration of nivolumab and ipilimumab with a planned switch in patients with advanced melanoma (CheckMate 064): an open-label, randomised, phase 2 trial. Jeffrey S Weber, Geoff Gibney, +14 authors, F Stephen Hodi. less Lancet Oncol, 2016 Jun 09; 17(7). PMID: 27269740 Free PMC article. Highly Cited.
In vivo blockade of CTLA-4 enhances the priming of responsive T cells but fails to prevent the induction of tumor antigen-specific tolerance. E M Sotomayor, I Borrello, +2 authors, E Tubb, J P Allison, H I Levitsky. less Proc Natl Acad Sci U S A, 1999 Sep 29; 96(20). PMID: 10500201 Free PMC article.
Phenotypic and functional changes of human melanoma xenografts induced by DNA hypomethylation: immunotherapeutic implications. Sandra Coral, Luca Sigalotti, +11 authors, Michele Maio. less J Cell Physiol, 2005 Oct 28; 207(1). PMID: 16252259
A systematic evaluation of abscopal responses following radiotherapy in patients with metastatic melanoma treated with ipilimumab. Ravi A Chandra, Tyler J Wilhite, +6 authors, Jonathan D Schoenfeld. less Oncoimmunology, 2015 Oct 10; 4(11). PMID: 26451318 Free PMC article. Highly Cited.
Abscopal effects of radiotherapy on advanced melanoma patients who progressed after ipilimumab immunotherapy. Antonio M Grimaldi, Ester Simeone, +15 authors, Paolo A Ascierto. less Oncoimmunology, 2014 Aug 02; 3. PMID: 25083318 Free PMC article. Highly Cited.
The evolution of checkpoint blockade as a cancer therapy: what's here, what's next? Daniel Sanghoon Shin, Antoni Ribas. Curr Opin Immunol, 2015 Jan 27; 33. PMID: 25621841 Highly Cited. Review.
Genetic basis for clinical response to CTLA-4 blockade in melanoma. Alexandra Snyder, Vladimir Makarov, +18 authors, Timothy A Chan. less N Engl J Med, 2014 Nov 20; 371(23). PMID: 25409260 Free PMC article. Highly Cited.
Ipilimumab alone or in combination with nivolumab after progression on anti-PD-1 therapy in advanced melanoma. Lisa Zimmer, Susmitha Apuri, +17 authors, Nikhil I Khushalani. less Eur J Cancer, 2017 Feb 20; 75. PMID: 28214657 Highly Cited.
Melanoma antigens are biomarkers for ipilimumab response. P Arenberger, A Fialova, +3 authors, M Arenbergerova. less J Eur Acad Dermatol Venereol, 2016 Aug 25; 31(2). PMID: 27557295
Experience in daily practice with ipilimumab for the treatment of patients with metastatic melanoma: an early increase in lymphocyte and eosinophil counts is associated with improved survival. J Delyon, C Mateus, +7 authors, C Robert. less Ann Oncol, 2013 Feb 27; 24(6). PMID: 23439861 Highly Cited.
Tumor stem cell antigens as consolidative active specific immunotherapy: a randomized phase II trial of dendritic cells versus tumor cells in patients with metastatic melanoma. Robert O Dillman, Andrew N Cornforth, +7 authors, James M Cubellis. less J Immunother, 2012 Sep 22; 35(8). PMID: 22996370
Three-year follow-up of advanced melanoma patients who received ipilimumab plus fotemustine in the Italian Network for Tumor Biotherapy (NIBIT)-M1 phase II study. A M Di Giacomo, P A Ascierto, +18 authors, M Maio. less Ann Oncol, 2014 Dec 30; 26(4). PMID: 25538176
Dendritic cell-based vaccine in advanced melanoma: update of clinical outcome. Laura Ridolfi, Massimiliano Petrini, +11 authors, Ruggero Ridolfi. less Melanoma Res, 2011 Sep 13; 21(6). PMID: 21909041
Targeted therapies in metastatic melanoma: toward a clinical breakthrough? Fanny Julia, Luc Thomas, Charles Dumontet, Stéphane Dalle. Anticancer Agents Med Chem, 2011 Jan 18; 10(9). PMID: 21235437 Review.
A phase I study of MEDI4736, NNT-PD-L1 antibody in patients with advanced solid tumors. Christoph C Zielinski. Transl Lung Cancer Res, 2015 Mar 26; 3(6). PMID: 25806335 Free PMC article.
Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma. Robert H I Andtbacka, Howard L Kaufman, +26 authors, Robert S Coffin. less J Clin Oncol, 2015 May 28; 33(25). PMID: 26014293 Highly Cited.
Indoleamine 2,3-dioxygenase and tumor-induced tolerance. David H Munn, Andrew L Mellor. J Clin Invest, 2007 May 04; 117(5). PMID: 17476344 Free PMC article. Highly Cited. Review.
Tumor immunotherapy in melanoma: strategies for overcoming mechanisms of resistance and escape. Maya Zigler, Gabriel J Villares, +2 authors, Dina C Lev, Vladislava O Melnikova, Menashe Bar-Eli. less Am J Clin Dermatol, 2008 Aug 23; 9(5). PMID: 18717605 Review.
Coinhibitory Pathways in the B7-CD28 Ligand-Receptor Family. Frank A Schildberg, Sarah R Klein, Gordon J Freeman, Arlene H Sharpe. Immunity, 2016 May 19; 44(5). PMID: 27192563 Free PMC article. Highly Cited. Review.
Hepatotoxicity with combination of vemurafenib and ipilimumab. Antoni Ribas, F Stephen Hodi, +2 authors, Margaret Callahan, Cyril Konto, Jedd Wolchok. less N Engl J Med, 2013 Apr 05; 368(14). PMID: 23550685 Highly Cited.
Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma. Antoni Ribas, Richard Kefford, +21 authors, Axel Hauschild. less J Clin Oncol, 2013 Jan 09; 31(5). PMID: 23295794 Free PMC article. Highly Cited.
Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. Julie R Brahmer, Scott S Tykodi, +23 authors, Jon M Wigginton. less N Engl J Med, 2012 Jun 05; 366(26). PMID: 22658128 Free PMC article. Highly Cited.
Novel technologies and emerging biomarkers for personalized cancer immunotherapy. Jianda Yuan, Priti S Hegde, +16 authors, Bernard A Fox. less J Immunother Cancer, 2016 Jan 21; 4. PMID: 26788324 Free PMC article. Highly Cited. Review.
Clinical activity and safety of Pembrolizumab in Ipilimumab pre-treated patients with uveal melanoma. Ioannis Karydis, Pui Ying Chan, +3 authors, Christian H Ottensmeier. less Oncoimmunology, 2016 Jul 29; 5(5). PMID: 27467964 Free PMC article.
Clinicopathologic features associated with efficacy and long-term survival in metastatic melanoma patients treated with BRAF or combined BRAF and MEK inhibitors. Alexander M Menzies, James S Wilmott, +9 authors, Georgina V Long. less Cancer, 2015 Jul 29; 121(21). PMID: 26218930
Improved survival with ipilimumab in patients with metastatic melanoma. F Stephen Hodi, Steven J O'Day, +26 authors, Walter J Urba. less N Engl J Med, 2010 Jun 08; 363(8). PMID: 20525992 Free PMC article. Highly Cited.
Combined treatment with dabrafenib and trametinib with immune-stimulating antibodies for BRAF mutant melanoma. Blanca Homet Moreno, Stephen Mok, +2 authors, Antoni Ribas. less Oncoimmunology, 2016 Sep 14; 5(7). PMID: 27622011 Free PMC article.
Prolonged Benefit from Ipilimumab Correlates with Improved Outcomes from Subsequent Pembrolizumab. Amanda Shreders, Richard Joseph, +5 authors, Douglas B Johnson. less Cancer Immunol Res, 2016 May 20; 4(7). PMID: 27197063 Free PMC article.
Immunological and biological changes during ipilimumab treatment and their potential correlation with clinical response and survival in patients with advanced melanoma. Ester Simeone, Giusy Gentilcore, +20 authors, Paolo A Ascierto. less Cancer Immunol Immunother, 2014 Apr 04; 63(7). PMID: 24695951 Highly Cited.
Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Jeffrey S Weber, Sandra P D'Angelo, +25 authors, James Larkin. less Lancet Oncol, 2015 Mar 22; 16(4). PMID: 25795410 Highly Cited.
Improved antitumor activity of immunotherapy with BRAF and MEK inhibitors in BRAF(V600E) melanoma. Siwen Hu-Lieskovan, Stephen Mok, +8 authors, Antoni Ribas. less Sci Transl Med, 2015 Mar 20; 7(279). PMID: 25787767 Free PMC article. Highly Cited.
gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. Douglas J Schwartzentruber, David H Lawson, +23 authors, Patrick Hwu. less N Engl J Med, 2011 Jun 03; 364(22). PMID: 21631324 Free PMC article. Highly Cited.
Long-term survival and immunological parameters in metastatic melanoma patients who responded to ipilimumab 10 mg/kg within an expanded access programme. Anna Maria Di Giacomo, Luana Calabrò, +10 authors, Michele Maio. less Cancer Immunol Immunother, 2013 Apr 18; 62(6). PMID: 23591982
Meta-analysis of phase II cooperative group trials in metastatic stage IV melanoma to determine progression-free and overall survival benchmarks for future phase II trials. Edward L Korn, Ping-Yu Liu, +11 authors, John M Kirkwood. less J Clin Oncol, 2008 Feb 01; 26(4). PMID: 18235113 Highly Cited.
Ipilimumab for Previously Untreated Unresectable Malignant Melanoma: A Critique of the Evidence. Christina Giannopoulou, Eleftherios Sideris, +3 authors, Claire McKenna. less Pharmacoeconomics, 2015 Jun 06; 33(12). PMID: 26043718 Review.
Dendritic cell vaccination in melanoma patients: From promising results to future perspectives. Steve Boudewijns, Martine Bloemendal, +2 authors, Gerty Schreibelt. less Hum Vaccin Immunother, 2016 Jun 21; 12(10). PMID: 27322496 Free PMC article.
Safety, efficacy, and biomarkers of nivolumab with vaccine in ipilimumab-refractory or -naive melanoma. Jeffrey S Weber, Ragini Reiney Kudchadkar, +11 authors, Y Ann Chen. less J Clin Oncol, 2013 Oct 23; 31(34). PMID: 24145345 Free PMC article. Highly Cited.
Ipilimumab and fotemustine in patients with advanced melanoma (NIBIT-M1): an open-label, single-arm phase 2 trial. Anna Maria Di Giacomo, Paolo A Ascierto, +14 authors, Michele Maio. less Lancet Oncol, 2012 Aug 17; 13(9). PMID: 22894884 Highly Cited.
Indoleamine 2,3-dioxygenase 1 (IDO1) is up-regulated in thyroid carcinoma and drives the development of an immunosuppressant tumor microenvironment. Sonia Moretti, Elisa Menicali, +19 authors, Efisio Puxeddu. less J Clin Endocrinol Metab, 2014 Feb 13; 99(5). PMID: 24517146
Immunosenescence and cancer. Tamas Fulop, Anis Larbi, +3 authors, Graham Pawelec. less Crit Rev Oncog, 2013 Jan 01; 18(6). PMID: 24579731 Review.
CTLA-4 and PD-1 Pathways: Similarities, Differences, and Implications of Their Inhibition. Elizabeth I Buchbinder, Anupam Desai. Am J Clin Oncol, 2015 Nov 13; 39(1). PMID: 26558876 Free PMC article. Highly Cited. Review.
Safety, correlative markers, and clinical results of adjuvant nivolumab in combination with vaccine in resected high-risk metastatic melanoma. Geoffrey T Gibney, Ragini R Kudchadkar, +13 authors, Jeffrey S Weber. less Clin Cancer Res, 2014 Dec 20; 21(4). PMID: 25524312 Free PMC article. Highly Cited.
Immune monitoring of the circulation and the tumor microenvironment in patients with regionally advanced melanoma receiving neoadjuvant ipilimumab. Ahmad A Tarhini, Howard Edington, +9 authors, John M Kirkwood. less PLoS One, 2014 Feb 06; 9(2). PMID: 24498358 Free PMC article. Highly Cited.
Abscopal Effects of Radiotherapy Are Enhanced by Combined Immunostimulatory mAbs and Are Dependent on CD8 T Cells and Crosspriming. María E Rodriguez-Ruiz, Inmaculada Rodriguez, +13 authors, Ignacio Melero. less Cancer Res, 2016 Aug 24; 76(20). PMID: 27550452 Highly Cited.
Nivolumab in previously untreated melanoma without BRAF mutation. Caroline Robert, Georgina V Long, +25 authors, Paolo A Ascierto. less N Engl J Med, 2014 Nov 18; 372(4). PMID: 25399552 Highly Cited.
Hepatic failure in a patient treated with dacarbazine (DTIC) for malignant melanoma. P J Frosch, B M Czarnetzki, +2 authors, E Macher, E Grundmann, I Gottschalk. less J Cancer Res Clin Oncol, 1979 Jan 01; 95(3). PMID: 528568
Efficacy and toxicity of treatment with the anti-CTLA-4 antibody ipilimumab in patients with metastatic melanoma after prior anti-PD-1 therapy. S Bowyer, P Prithviraj, +17 authors, O Klein. less Br J Cancer, 2016 Apr 29; 114(10). PMID: 27124339 Free PMC article.
Extended dose ipilimumab with a peptide vaccine: immune correlates associated with clinical benefit in patients with resected high-risk stage IIIc/IV melanoma. Amod A Sarnaik, Bin Yu, +9 authors, Jeffrey S Weber. less Clin Cancer Res, 2010 Nov 26; 17(4). PMID: 21106722 Free PMC article.
Combining talimogene laherparepvec with immunotherapies in melanoma and other solid tumors. Reinhard Dummer, Christoph Hoeller, Isabella Pezzani Gruter, Olivier Michielin. Cancer Immunol Immunother, 2017 Feb 27; 66(6). PMID: 28238174 Free PMC article. Review.
Comparison of dabrafenib and trametinib combination therapy with vemurafenib monotherapy on health-related quality of life in patients with unresectable or metastatic cutaneous BRAF Val600-mutation-positive melanoma (COMBI-v): results of a phase 3, open-label, randomised trial. Jean Jacques Grob, Mayur M Amonkar, +22 authors, Caroline Robert. less Lancet Oncol, 2015 Oct 05; 16(13). PMID: 26433819
Programmed Death-Ligand 1 Expression and Response to the Anti-Programmed Death 1 Antibody Pembrolizumab in Melanoma. Adil I Daud, Jedd D Wolchok, +21 authors, Omid Hamid. less J Clin Oncol, 2016 Nov 20; 34(34). PMID: 27863197 Free PMC article. Highly Cited.
Heterogeneity of Programmed Cell Death Ligand 1 Expression in Multifocal Lung Cancer. Aaron S Mansfield, Stephen J Murphy, +4 authors, Marie Christine Aubry. less Clin Cancer Res, 2015 Dec 17; 22(9). PMID: 26667490 Free PMC article.
Analysis of Immune Signatures in Longitudinal Tumor Samples Yields Insight into Biomarkers of Response and Mechanisms of Resistance to Immune Checkpoint Blockade. Pei-Ling Chen, Whijae Roh, +41 authors, Jennifer A Wargo. less Cancer Discov, 2016 Jun 16; 6(8). PMID: 27301722 Free PMC article. Highly Cited.
Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab. A M Menzies, D B Johnson, +17 authors, G V Long. less Ann Oncol, 2016 Oct 01; 28(2). PMID: 27687304 Highly Cited.
Lactate dehydrogenase as a selection criterion for ipilimumab treatment in metastatic melanoma. Sander Kelderman, Bianca Heemskerk, +18 authors, Christian U Blank. less Cancer Immunol Immunother, 2014 Mar 13; 63(5). PMID: 24609989 Highly Cited.
Combining targeted therapy with immunotherapy in BRAF-mutant melanoma: promise and challenges. Siwen Hu-Lieskovan, Lidia Robert, Blanca Homet Moreno, Antoni Ribas. J Clin Oncol, 2014 Jun 25; 32(21). PMID: 24958825 Free PMC article. Highly Cited. Review.
Targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4): a novel strategy for the treatment of melanoma and other malignancies. Steven J O'Day, Omid Hamid, Walter J Urba. Cancer, 2007 Nov 16; 110(12). PMID: 18000991 Review.
PD-1 blockade induces responses by inhibiting adaptive immune resistance. Paul C Tumeh, Christina L Harview, +23 authors, Antoni Ribas. less Nature, 2014 Nov 28; 515(7528). PMID: 25428505 Free PMC article. Highly Cited.
Preclinical evidence that PD1 blockade cooperates with cancer vaccine TEGVAX to elicit regression of established tumors. Juan Fu, Ian-James Malm, +3 authors, Young J Kim. less Cancer Res, 2014 May 09; 74(15). PMID: 24812273 Free PMC article.
Melanoma-specific MHC-II expression represents a tumour-autonomous phenotype and predicts response to anti-PD-1/PD-L1 therapy. Douglas B Johnson, Monica V Estrada, +18 authors, Justin M Balko. less Nat Commun, 2016 Jan 30; 7. PMID: 26822383 Free PMC article. Highly Cited.
Antigenic properties of methylcholanthrene-induced tumors in mice of the strain of origin. E J FOLEY. Cancer Res, 1953 Dec 01; 13(12). PMID: 13116120 Highly Cited.
Immunotherapy and chemotherapy--a practical partnership. Richard A Lake, Bruce W S Robinson. Nat Rev Cancer, 2005 May 03; 5(5). PMID: 15864281 Highly Cited. Review.
Indoleamine 2,3-dioxygenase expression in human cancers: clinical and immunologic perspectives. Jessica Godin-Ethier, Laïla-Aïcha Hanafi, Ciriaco A Piccirillo, Réjean Lapointe. Clin Cancer Res, 2011 Nov 10; 17(22). PMID: 22068654 Highly Cited. Review.
Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial. Antoni Ribas, Igor Puzanov, +33 authors, Adil Daud. less Lancet Oncol, 2015 Jun 28; 16(8). PMID: 26115796 Free PMC article. Highly Cited.
Combining radiation and immunotherapy: a new systemic therapy for solid tumors? Chad Tang, Xiaohong Wang, +14 authors, James W Welsh. less Cancer Immunol Res, 2014 Sep 05; 2(9). PMID: 25187273 Free PMC article. Highly Cited. Review.
Personalised medicine: Development and external validation of a prognostic model for metastatic melanoma patients treated with ipilimumab. S Valpione, C Martinoli, +8 authors, V Chiarion-Sileni. less Eur J Cancer, 2015 Aug 01; 51(14). PMID: 26227432
PD-L1 Expression as a Predictive Biomarker in Cancer Immunotherapy. Sandip Pravin Patel, Razelle Kurzrock. Mol Cancer Ther, 2015 Feb 20; 14(4). PMID: 25695955 Highly Cited. Review.
Regulation of PD-L1: a novel role of pro-survival signalling in cancer. J Chen, C C Jiang, L Jin, X D Zhang. Ann Oncol, 2015 Dec 19; 27(3). PMID: 26681673 Highly Cited. Review.
Does It MEK a Difference? Understanding Immune Effects of Targeted Therapy. Zachary A Cooper, Alexandre Reuben, Jacob Austin-Breneman, Jennifer A Wargo. Clin Cancer Res, 2015 May 31; 21(14). PMID: 26025561 Free PMC article.
Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. Manish J Butte, Mary E Keir, +2 authors, Theresa B Phamduy, Arlene H Sharpe, Gordon J Freeman. less Immunity, 2007 Jul 17; 27(1). PMID: 17629517 Free PMC article. Highly Cited.
Efficacy and safety of ipilimumab in elderly patients with pretreated advanced melanoma treated at Italian centres through the expanded access programme. Vanna Chiarion Sileni, Jacopo Pigozzo, +17 authors, Paola Queirolo. less J Exp Clin Cancer Res, 2014 Apr 09; 33. PMID: 24708900 Free PMC article.
MEK Inhibitors in the Treatment of Metastatic Melanoma and Solid Tumors. Antonio M Grimaldi, Ester Simeone, +3 authors, Paolo A Ascierto. less Am J Clin Dermatol, 2017 May 26; 18(6). PMID: 28537004 Review.
Durable benefit and the potential for long-term survival with immunotherapy in advanced melanoma. David McDermott, Celeste Lebbé, +5 authors, Charles M Balch. less Cancer Treat Rev, 2014 Jul 26; 40(9). PMID: 25060490 Highly Cited. Review.
Hepatic vascular lesions associated with dacarbazine treatment. M A Greenstone, P M Dowd, D P Mikhailidis, P J Scheuer. Br Med J (Clin Res Ed), 1981 May 30; 282(6278). PMID: 6786601 Free PMC article.
Baseline neutrophils and derived neutrophil-to-lymphocyte ratio: prognostic relevance in metastatic melanoma patients receiving ipilimumab. P F Ferrucci, P A Ascierto, +15 authors, C Martinoli. less Ann Oncol, 2016 Jan 24; 27(4). PMID: 26802161 Highly Cited.
Dacarbazine (DTIC)-induced human liver damage light and electron-microscopic findings. H Dancygier, U Runne, +2 authors, U Leuschner, R Milbradt, M Classen. less Hepatogastroenterology, 1983 Jun 01; 30(3). PMID: 6884975
Optimization of immunotherapy in elderly cancer patients. Kei Tomihara, Tyler J Curiel, Bin Zhang. Crit Rev Oncog, 2013 Jan 01; 18(6). PMID: 24579736 Free PMC article. Review.
A systemic complete response of metastatic melanoma to local radiation and immunotherapy. Susan M Hiniker, Daniel S Chen, +5 authors, Susan J Knox. less Transl Oncol, 2013 Jan 17; 5(6). PMID: 23323154 Free PMC article. Highly Cited.
Immunologic correlates of the abscopal effect in a patient with melanoma. Michael A Postow, Margaret K Callahan, +18 authors, Jedd D Wolchok. less N Engl J Med, 2012 Mar 09; 366(10). PMID: 22397654 Free PMC article. Highly Cited.
Ipilimumab after progression on anti-PD-1 treatment in advanced melanoma. Francisco Aya, Lydia Gaba, +4 authors, Ana Arance. less Future Oncol, 2016 Sep 02; 12(23). PMID: 27581765
Biomarkers for immunostimulatory monoclonal antibodies in combination strategies for melanoma and other tumor types. Paolo A Ascierto, Michael Kalos, +2 authors, David A Schaer, Margaret K Callahan, Jedd D Wolchok. less Clin Cancer Res, 2013 Mar 06; 19(5). PMID: 23460532 Highly Cited.
Analysis of the Abscopal Effect With Anti-PD1 Therapy in Patients With Metastatic Solid Tumors. Jéssica Ribeiro Gomes, Rafael A Schmerling, +5 authors, Antônio C Buzaid. less J Immunother, 2016 Oct 16; 39(9). PMID: 27741091
High neutrophil to lymphocyte ratio measured before starting ipilimumab treatment is associated with reduced overall survival in patients with melanoma. J Zaragoza, A Caille, +4 authors, L Machet. less Br J Dermatol, 2015 Sep 08; 174(1). PMID: 26343230
Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Haidong Dong, Scott E Strome, +10 authors, Lieping Chen. less Nat Med, 2002 Jul 02; 8(8). PMID: 12091876 Highly Cited.
Dacarbazine (DTIC) versus vaccination with autologous peptide-pulsed dendritic cells (DC) in first-line treatment of patients with metastatic melanoma: a randomized phase III trial of the DC study group of the DeCOG. D Schadendorf, S Ugurel, +18 authors, DC study group of the DeCOG. less Ann Oncol, 2006 Jan 19; 17(4). PMID: 16418308 Highly Cited.
Phase II Study of Autologous Monocyte-Derived mRNA Electroporated Dendritic Cells (TriMixDC-MEL) Plus Ipilimumab in Patients With Pretreated Advanced Melanoma. Sofie Wilgenhof, Jurgen Corthals, +5 authors, Bart Neyns. less J Clin Oncol, 2016 Mar 02; 34(12). PMID: 26926680 Highly Cited.
An immune-active tumor microenvironment favors clinical response to ipilimumab. Rui-Ru Ji, Scott D Chasalow, +9 authors, Vafa Shahabi. less Cancer Immunol Immunother, 2011 Dec 08; 61(7). PMID: 22146893 Highly Cited.
Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. Jedd D Wolchok, Vanna Chiarion-Sileni, +30 authors, James Larkin. less N Engl J Med, 2017 Sep 12; 377(14). PMID: 28889792 Free PMC article. Highly Cited.
Developmental biology. Pluripotent chromatin state. Andrew S Chi, Bradley E Bernstein. Science, 2009 Jan 10; 323(5911). PMID: 19131621 Free PMC article.
Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. James Larkin, Vanna Chiarion-Sileni, +28 authors, Jedd D Wolchok. less N Engl J Med, 2015 Jun 02; 373(1). PMID: 26027431 Free PMC article. Highly Cited.
Management of immune checkpoint blockade dysimmune toxicities: a collaborative position paper. S Champiat, O Lambotte, +20 authors, A Marabelle. less Ann Oncol, 2015 Dec 31; 27(4). PMID: 26715621 Highly Cited. Review.
Fotemustine compared with dacarbazine in patients with disseminated malignant melanoma: a phase III study. M F Avril, S Aamdal, +17 authors, Y Menu. less J Clin Oncol, 2004 Mar 17; 22(6). PMID: 15020614 Highly Cited.
Neoantigens in cancer immunotherapy. Ton N Schumacher, Robert D Schreiber. Science, 2015 Apr 04; 348(6230). PMID: 25838375 Highly Cited. Review.
Efficacy and safety of ipilimumab in metastatic melanoma patients surviving more than 2 years following treatment in a phase III trial (MDX010-20). D McDermott, J Haanen, +3 authors, T-T Chen, P Lorigan, S O'Day, MDX010-20 investigators. less Ann Oncol, 2013 Aug 15; 24(10). PMID: 23942774
Evaluation of tumor-specific promoter activities in melanoma. B Lu, S K Makhija, +9 authors, Z B Zhu. less Gene Ther, 2005 Feb 08; 12(4). PMID: 15696177
Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. Caroline Robert, Luc Thomas, +21 authors, Jedd D Wolchok. less N Engl J Med, 2011 Jun 07; 364(26). PMID: 21639810 Highly Cited.
Radiation Therapy Plus Anti-Programmed Death Ligand 1 Immunotherapy: A Review on Overall Survival. Elizabeth Marie Krcik. Radiol Technol, 2016 Sep 08; 88(1). PMID: 27601709 Review.
Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma. Tyler R Simpson, Fubin Li, +11 authors, Sergio A Quezada. less J Exp Med, 2013 Jul 31; 210(9). PMID: 23897981 Free PMC article. Highly Cited.
Cytokines can counteract the inhibitory effect of MEK-i on NK-cell function. Claudia Manzini, Roberta Venè, +8 authors, Gabriella Pietra. less Oncotarget, 2016 Aug 27; 7(38). PMID: 27563819 Free PMC article.
Pembrolizumab versus Ipilimumab in Advanced Melanoma. Caroline Robert, Jacob Schachter, +20 authors, KEYNOTE-006 investigators. less N Engl J Med, 2015 Apr 22; 372(26). PMID: 25891173 Highly Cited.
CANCER IMMUNOLOGY. The "cancer immunogram". Christian U Blank, John B Haanen, Antoni Ribas, Ton N Schumacher. Science, 2016 May 07; 352(6286). PMID: 27151852 Highly Cited.
Targeting immunosupportive cancer therapies: accentuate the positive, eliminate the negative. Karl S Peggs, Neil H Segal, James P Allison. Cancer Cell, 2007 Sep 06; 12(3). PMID: 17785201
Increases in Absolute Lymphocytes and Circulating CD4+ and CD8+ T Cells Are Associated with Positive Clinical Outcome of Melanoma Patients Treated with Ipilimumab. Alexander Martens, Kilian Wistuba-Hamprecht, +15 authors, Benjamin Weide. less Clin Cancer Res, 2016 May 14; 22(19). PMID: 27169993 Free PMC article. Highly Cited.
Upregulated expression of indoleamine 2, 3-dioxygenase in primary breast cancer correlates with increase of infiltrated regulatory T cells in situ and lymph node metastasis. Jinpu Yu, Jingyan Sun, +5 authors, Xiubao Ren. less Clin Dev Immunol, 2011 Nov 24; 2011. PMID: 22110525 Free PMC article.
Current systemic therapy for metastatic melanoma. Sanjiv S Agarwala. Expert Rev Anticancer Ther, 2009 May 19; 9(5). PMID: 19445576 Review.
Severe gastrointestinal toxicity with administration of trametinib in combination with dabrafenib and ipilimumab. David R Minor, Igor Puzanov, +2 authors, Margaret K Callahan, Bruce A Hug, Axel Hoos. less Pigment Cell Melanoma Res, 2015 May 23; 28(5). PMID: 25996827 Free PMC article.
Mechanism of tumor rejection with doublets of CTLA-4, PD-1/PD-L1, or IDO blockade involves restored IL-2 production and proliferation of CD8(+) T cells directly within the tumor microenvironment. Stefani Spranger, Holly K Koblish, +3 authors, Thomas F Gajewski. less J Immunother Cancer, 2014 May 16; 2. PMID: 24829760 Free PMC article. Highly Cited.
Epigenetics of human cutaneous melanoma: setting the stage for new therapeutic strategies. Luca Sigalotti, Alessia Covre, +7 authors, Michele Maio. less J Transl Med, 2010 Jun 15; 8. PMID: 20540720 Free PMC article.
Radiation and checkpoint blockade immunotherapy: radiosensitisation and potential mechanisms of synergy. Andrew B Sharabi, Michael Lim, Theodore L DeWeese, Charles G Drake. Lancet Oncol, 2015 Oct 05; 16(13). PMID: 26433823 Highly Cited. Review.
Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Catherine Uyttenhove, Luc Pilotte, +5 authors, Benoît J Van den Eynde. less Nat Med, 2003 Sep 23; 9(10). PMID: 14502282 Highly Cited.
Changes in miRNA expression in solid tumors: an miRNA profiling in melanomas. Viktor Molnár, Viola Tamási, +2 authors, Beáta Bakos, Zoltán Wiener, András Falus. less Semin Cancer Biol, 2008 Feb 26; 18(2). PMID: 18296065 Review.
The perspective of immunotherapy: new molecules and new mechanisms of action in immune modulation. Christian U Blank. Curr Opin Oncol, 2014 Jan 16; 26(2). PMID: 24424272 Review.

Citedby
The role of routine imaging in pediatric cutaneous melanoma. Hadeel Halalsheh, Sue C Kaste, +6 authors, Alberto Pappo. less Pediatr Blood Cancer, 2018 Aug 21; 65(12). PMID: 30124237 Free PMC article.
Homologous Recombination Repair Deficiency and the Immune Response in Breast Cancer: A Literature Review. B Pellegrino, A Musolino, +6 authors, C Solinas. less Transl Oncol, 2020 Jan 07; 13(2). PMID: 31901781 Free PMC article. Review.
microRNA-134 inhibits melanoma growth and metastasis by negatively regulating collagen triple helix repeat containing-1 (CTHRC1). Yuan Li, Yong Fu, +5 authors, Chong Ma. less Int J Clin Exp Pathol, 2018 Sep 01; 11(9). PMID: 31949828 Free PMC article.
Tumor Time-Course Predicts Overall Survival in Non-Small Cell Lung Cancer Patients Treated with Atezolizumab: Dependency on Follow-Up Time. Ida Netterberg, René Bruno, +4 authors, Lena E Friberg. less CPT Pharmacometrics Syst Pharmacol, 2020 Jan 29; 9(2). PMID: 31991070 Free PMC article.
Preclinical and clinical combination therapies in the treatment of anaplastic thyroid cancer. Daniela Gentile, Paola Orlandi, Marta Banchi, Guido Bocci. Med Oncol, 2020 Feb 29; 37(3). PMID: 32108281 Review.
A QSP Model for Predicting Clinical Responses to Monotherapy, Combination and Sequential Therapy Following CTLA-4, PD-1, and PD-L1 Checkpoint Blockade. Oleg Milberg, Chang Gong, +6 authors, Aleksander S Popel. less Sci Rep, 2019 Aug 04; 9(1). PMID: 31375756 Free PMC article.
Response and outcomes after anti-CTLA4 versus anti-PD1 combined with stereotactic body radiation therapy for metastatic non-small cell lung cancer: retrospective analysis of two single-institution prospective trials. Dawei Chen, Hari Menon, +8 authors, James Welsh. less J Immunother Cancer, 2020 Jan 31; 8(1). PMID: 31996395 Free PMC article.
Current Advances in the Treatment of BRAF-Mutant Melanoma. Hima Patel, Nour Yacoub, +4 authors, Joan T Garrett. less Cancers (Basel), 2020 Feb 26; 12(2). PMID: 32092958 Free PMC article. Review.
The promising immune checkpoint LAG-3: from tumor microenvironment to cancer immunotherapy. Long Long, Xue Zhang, +4 authors, Honglei Chen. less Genes Cancer, 2019 Jan 04; 9(5-6). PMID: 30603054 Free PMC article. Highly Cited. Review.
Combination treatment with nivolumab and Rigvir of a progressive stage IIC skin melanoma patient. Linda Brokāne, Inta Jaunalksne, +4 authors, Pēteris Alberts. less Clin Case Rep, 2019 Jun 12; 7(6). PMID: 31183092 Free PMC article.
Intratumoural immunotherapies for unresectable and metastatic melanoma: current status and future perspectives. Mark R Middleton, Christoph Hoeller, +4 authors, Axel Hauschild. less Br J Cancer, 2020 Jul 28; 123(6). PMID: 32713938 Free PMC article. Review.
The Influence of Tumor Microenvironment on Immune Escape of Melanoma. Aleksandra Simiczyjew, Ewelina Dratkiewicz, +3 authors, Dorota Nowak. less Int J Mol Sci, 2020 Nov 12; 21(21). PMID: 33171792 Free PMC article. Review.
Natural Health Products (NHP's) and Natural Compounds as Therapeutic Agents for the Treatment of Cancer; Mechanisms of Anti-Cancer Activity of Natural Compounds and Overall Trends. Benjamin Scaria, Siddhartha Sood, +8 authors, Siyaram Pandey. less Int J Mol Sci, 2020 Nov 15; 21(22). PMID: 33187200 Free PMC article. Review.
Vaccines as an Integral Component of Cancer Immunotherapy. Jeffrey Schlom, James L Gulley. JAMA, 2018 Nov 13; 320(21). PMID: 30419097 Free PMC article.
From Tumor Immunology to Immunotherapy in Gastric and Esophageal Cancer. David Vrána, Marcel Matzenauer, +6 authors, Janusz Jankowski. less Int J Mol Sci, 2018 Dec 24; 20(1). PMID: 30577521 Free PMC article. Review.
Advances in the Understanding of Skin Cancer: Ultraviolet Radiation, Mutations, and Antisense Oligonucleotides as Anticancer Drugs. Kateryna V Laikova, Volodymyr V Oberemok, +13 authors, Anatoly V Kubyshkin. less Molecules, 2019 Apr 20; 24(8). PMID: 30999681 Free PMC article. Review.
Serine-Threonine Kinase TAO3-Mediated Trafficking of Endosomes Containing the Invadopodia Scaffold TKS5α Promotes Cancer Invasion and Tumor Growth. Shinji Iizuka, Manuela Quintavalle, +12 authors, Sara A Courtneidge. less Cancer Res, 2021 Jan 09; 81(6). PMID: 33414172 Free PMC article.
Recent Progress in the Synergistic Combination of Nanoparticle-Mediated Hyperthermia and Immunotherapy for Treatment of Cancer. Zachary R Stephen, Miqin Zhang. Adv Healthc Mater, 2020 Nov 26; 10(2). PMID: 33236511 Free PMC article. Review.
Talimogene laherparepvec upregulates immune-cell populations in non-injected lesions: findings from a phase II, multicenter, open-label study in patients with stage IIIB-IVM1c melanoma. Josep Malvehy, Igor Samoylenko, +8 authors, Helen Gogas. less J Immunother Cancer, 2021 Apr 01; 9(3). PMID: 33785610 Free PMC article.
Recent Advances on Immune Targeted Therapy of Colorectal Cancer Using bi-Specific Antibodies and Therapeutic Vaccines. Ali Azadi, Alireza Golchini, +4 authors, Shirin Eyvazi. less Biol Proced Online, 2021 Jul 02; 23(1). PMID: 34193050 Free PMC article. Review.
Development and Validation of a Prognostic Gene Signature Correlated With M2 Macrophage Infiltration in Esophageal Squamous Cell Carcinoma. Jiannan Yao, Ling Duan, +8 authors, Yang Ge. less Front Oncol, 2021 Dec 21; 11. PMID: 34926275 Free PMC article.
Can Immune Suppression and Epigenome Regulation in Placenta Offer Novel Insights into Cancer Immune Evasion and Immunotherapy Resistance? Sultana Mehbuba Hossain, Chiemi F Lynch-Sutherland, +2 authors, Michael R Eccles. less Epigenomes, 2021 Dec 31; 5(3). PMID: 34968365 Free PMC article. Review.
The Interplay between Tumour Microenvironment Components in Malignant Melanoma. Cornelia Amalinei, Adriana Grigoraș, +3 authors, Raluca Anca Balan. less Medicina (Kaunas), 2022 Mar 27; 58(3). PMID: 35334544 Free PMC article. Review.
Melanoma, Melanin, and Melanogenesis: The Yin and Yang Relationship. Radomir M Slominski, Tadeusz Sarna, +3 authors, Andrzej T Slominski. less Front Oncol, 2022 Apr 02; 12. PMID: 35359389 Free PMC article. Review.

BioKDE: Biomedical Knowledge Discovery Engine

Abstract

Other Links