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Melanoma—Time to fast or time to feast? An interplay between PPARs, metabolism and immunity
Author(s) -
Grabacka Maja,
Plonka Przemyslaw M.,
Reiss Krzysztof
Publication year - 2020
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.14072
Subject(s) - melanoma , coactivator , tumor microenvironment , biology , cancer research , nuclear receptor , immune checkpoint , peroxisome proliferator activated receptor , immune system , ampk , pi3k/akt/mtor pathway , inflammation , catabolism , mechanistic target of rapamycin , tumor progression , cancer , microbiology and biotechnology , immunology , receptor , metabolism , protein kinase a , signal transduction , kinase , endocrinology , immunotherapy , transcription factor , biochemistry , genetics , gene
Development and progression of melanoma can be accelerated by intensification of particular metabolic pathways, such as aerobic glycolysis and avid amino acid catabolism, and is accompanied by aberrant immune responses within the tumor microenvironment. Contrary to other cancer types, melanoma reveals some unique tissue‐specific features, such as melanogenesis, which is intertwined with metabolism. Nuclear peroxisome proliferator‐activated receptors (PPARs) take part in regulation of systemic and cellular metabolism, inflammation and melanogenesis. They appear as a focal regulatory point for these three distinct processes by occupying the intersection among AMP‐dependent protein kinase (AMPK), mammalian target of rapamycin (mTOR) and PPAR gamma coactivator 1‐alpha (PGC‐1α) signalling pathways. When deregulated, they may accelerate melanoma malignant growth. Presenting the contribution of PPARα and PPARγ in melanoma biology, we attempt to ask how two contrasting metabolic states: obesity and fasting, can change progression of the disease and possible outcome of the treatment. This short essay is aimed to provoke a discussion about some practical implications for melanoma prevention and treatment, especially: how metabolic manipulation may be exploited to overcome immunosuppression and support immune checkpoint blockade efficacy.