. 2022 Feb; 22(4):195-207.
doi: 10.1038/s41568-022-00442-9.

Mechanisms of immune activation and regulation: lessons from melanoma

Shelly Kalaora 1 Adi Nagler 1 Jennifer A Wargo 2 Yardena Samuels 3 
  • PMID: 35105962
  •     183 References


Melanoma, a skin cancer that develops from pigment cells, has been studied intensively, particularly in terms of the immune response to tumours, and has been used as a model for the development of immunotherapy. This is due, in part, to the high mutational burden observed in melanomas, which increases both their immunogenicity and the infiltration of immune cells into the tumours, compared with other types of cancers. The immune response to melanomas involves a complex set of components and interactions. As the tumour evolves, it accumulates an increasing number of genetic and epigenetic alterations, some of which contribute to the immunogenicity of the tumour cells and the infiltration of immune cells. However, tumour evolution also enables the development of resistance mechanisms, which, in turn, lead to tumour immune escape. Understanding the interactions between melanoma tumour cells and the immune system, and the evolving changes within the melanoma tumour cells, the immune system and the microenvironment, is essential for the development of new cancer therapies. However, current research suggests that other extrinsic factors, such as the microbiome, may play a role in the immune response to melanomas. Here, we review the mechanisms underlying the immune response in the tumour and discuss recent advances as well as strategies for treatment development.

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Science, 2017 Nov 04; 359(6371). PMID: 29097493    Free PMC article.
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Science, 2017 Nov 04; 359(6371). PMID: 29097494
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Ayelet Sivan, Leticia Corrales, +9 authors, Thomas F Gajewski.
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Marie Vétizou, Jonathan M Pitt, +35 authors, Laurence Zitvogel.
Science, 2015 Nov 07; 350(6264). PMID: 26541610    Free PMC article.
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Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients.
Erez N Baruch, Ilan Youngster, +29 authors, Ben Boursi.
Science, 2020 Dec 12; 371(6529). PMID: 33303685
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Nature, 2019 Jan 25; 565(7741). PMID: 30675064
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Nature, 2020 Mar 28; 579(7800). PMID: 32214244    Free PMC article.
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Nancy E Thomas, Klaus J Busam, +20 authors, Marianne Berwick.
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Paul C Tumeh, Christina L Harview, +23 authors, Antoni Ribas.
Nature, 2014 Nov 28; 515(7528). PMID: 25428505    Free PMC article.
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Tumor and Microenvironment Evolution during Immunotherapy with Nivolumab.
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Cell, 2017 Oct 17; 171(4). PMID: 29033130    Free PMC article.
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N Engl J Med, 2012 Jun 05; 366(26). PMID: 22658127    Free PMC article.
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Jedd D Wolchok, Harriet Kluger, +21 authors, Mario Sznol.
N Engl J Med, 2013 Jun 04; 369(2). PMID: 23724867    Free PMC article.
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N Engl J Med, 2014 Nov 18; 372(4). PMID: 25399552
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Cancer Cell, 2020 Sep 12; 38(4). PMID: 32916126    Free PMC article.
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Genomic and Transcriptomic Features of Response to Anti-PD-1 Therapy in Metastatic Melanoma.
Willy Hugo, Jesse M Zaretsky, +15 authors, Roger S Lo.
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Publisher Correction: Combined BRAF and MEK inhibition with PD-1 blockade immunotherapy in BRAF-mutant melanoma.
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Nat Med, 2019 Jul 04; 25(8). PMID: 31267021
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Nat Med, 2019 Jun 07; 25(6). PMID: 31171878
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Atezolizumab plus cobimetinib and vemurafenib in BRAF-mutated melanoma patients.
Ryan J Sullivan, Omid Hamid, +13 authors, Patrick Hwu.
Nat Med, 2019 Jun 07; 25(6). PMID: 31171876
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Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy.
Antoni Ribas, Reinhard Dummer, +17 authors, Georgina V Long.
Cell, 2017 Sep 09; 170(6). PMID: 28886381    Free PMC article.
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Nat Commun, 2017 Nov 14; 8(1). PMID: 29129918    Free PMC article.
An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma.
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Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer.
Christina Twyman-Saint Victor, Andrew J Rech, +22 authors, Andy J Minn.
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Cancer regression in patients after transfer of genetically engineered lymphocytes.
Richard A Morgan, Mark E Dudley, +13 authors, Steven A Rosenberg.
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CRISPR-engineered T cells in patients with refractory cancer.
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Jennifer A Wargo.
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Steven A Rosenberg.
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Anti-NKG2A mAb Is a Checkpoint Inhibitor that Promotes Anti-tumor Immunity by Unleashing Both T and NK Cells.
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Immunity, 2018 Mar 22; 48(3). PMID: 29562195
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Prospects for gene-engineered T cell immunotherapy for solid cancers.
Christopher A Klebanoff, Steven A Rosenberg, Nicholas P Restifo.
Nat Med, 2016 Jan 07; 22(1). PMID: 26735408    Free PMC article.
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Antonia L Pritchard, Marcus L Hastie, +3 authors, Nicholas K Hayward.
Pigment Cell Melanoma Res, 2015 Feb 04; 28(3). PMID: 25645385
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Nat Med, 2014 Dec 23; 21(1). PMID: 25531942
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Dissection of T-cell antigen specificity in human melanoma.
Rikke Sick Andersen, Charlotte Albæk Thrue, +7 authors, Sine Reker Hadrup.
Cancer Res, 2012 Feb 09; 72(7). PMID: 22311675
TIL therapy broadens the tumor-reactive CD8(+) T cell compartment in melanoma patients.
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Oncoimmunology, 2012 Jul 04; 1(4). PMID: 22754759    Free PMC article.
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Stavros Bashiardes, Gili Zilberman-Schapira, Eran Elinav.
Bioinform Biol Insights, 2016 Apr 30; 10. PMID: 27127406    Free PMC article.
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Ongoing revolution in bacteriology: routine identification of bacteria by matrix-assisted laser desorption ionization time-of-flight mass spectrometry.
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Clin Infect Dis, 2009 Jul 09; 49(4). PMID: 19583519
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Matrix-assisted laser desorption ionization-time of flight mass spectrometry: a fundamental shift in the routine practice of clinical microbiology.
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Highly Cited. Review.