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TUMOUR IMMUNOLOGY

Helping tumour antigens to the surface

Nature Reviews Cancer volume 19, page 608 (2019)Cite this article

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Omics-based analyses, mainly involving transcriptomics, have amplified our understanding of the mutational profile of melanoma and the make-up of tumour-infiltrating immune cell populations. Now, using high-resolution proteomic analysis of clinical samples from patients with advanced melanoma, Harel et al. show that the metabolic state of melanoma is associated with response to immunotherapies.

Next, the researchers performed functional cluster analysis based on Kyoto Encyclopaedia Genes and Genomes pathway annotations. In both cohorts, high levels of metabolic proteins (specifically, proteins of the tricarboxylic acid cycle, fatty acid oxidation and ketone body metabolism) as well as antigen presentation-related proteins (including type I and type II interferon (IFN) signalling proteins) dominated the responder group. By contrast, spliceosome and RNA metabolism-related proteins dominated the non-responder group. The dominance of mitochondrial metabolism and IFN signalling-related pathways in responders was also apparent when both cohorts were pooled and subjected to weighted gene correlation network analysis, and on the RNA level based on published RNA sequencing datasets of similar cohorts (although, here, the enrichment was lower than at the proteome level).

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References

Original article

  • Harel, M. et al. Proteomics of melanoma response to immunotherapy reveals mitochondrial dependence. Cell 179, 236–250 (2019)

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  1. Nature Reviews Cancer http://www.nature.com/nrc/

    Ulrike Harjes

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  1. Ulrike Harjes
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Correspondence to Ulrike Harjes.

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Harjes, U. Helping tumour antigens to the surface. Nat Rev Cancer 19, 608 (2019). https://doi.org/10.1038/s41568-019-0212-y

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