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Review
. 2018 Jan 3;9(15):12452-12470.
doi: 10.18632/oncotarget.23746. eCollection 2018 Feb 23.

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
Review

Current status and perspectives in immunotherapy for metastatic melanoma

Riccardo Marconcini et al. Oncotarget. .

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.

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Conflict of interest statement

CONFLICTS OF INTEREST R.M. has received payment for consultancy and honoraria for speaking from BMS, MSD, Novartis, Roche. The other authors declare no competing interests.

Figures

Figure 1
Figure 1. Mechanisms of action of anti-CTLA4, anti-PD-1, and anti-PD-L1
Antigen Presenting Cells interact with Lymphocyte: the immunological synapses is composed by activation signals (exemplified in yellow) and inhibitory signals like CTLA4 (exemplified in red).CTLA4 is a target of AtiCTLA4 drugs. Activated Lymphocyte migrate to melanoma cells. The interaction between PDL1 (expressed by melanoma cells) and PD1 (expressed by Lymphocyte) causes Lymphocyte anergy. AntPD1 and ANtPDL1 drugs prevent this interaction.
Figure 2
Figure 2. New Agent for combinations with immunotherapy: meccanism of action
(1) BRAF end MEK inhibitors block MAPKinasi pathway (indicated with RAS, BRAF, MEK, ERK in the figure). (2) Epigenetic drugs modulates proteins expression trough an alteration in usual DNA-RNA-protein sequence, and causing immnostimulation (see text). (3) Antigen (exemplified with triangles) vaccination: Vaccination stimulate dendritic cells to activate immunoresponse against melanoma cell. (4) IDO inhibitors repress T cell suppression by blocking tryptophan conversion. T VEC therapy cause local immunoinfiltration by causing local G CSF production.
See this image and copyright information in PMC

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