Proteomics

Dataset Information

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Immunoproteasome expression is associated with better prognosis and response to checkpoint therapies in melanoma


ABSTRACT: Predicting the outcome of immunotherapy treatment in melanoma patients is challenging. Alterations in genes involved in antigen presentation and the interferon gamma (IFN) pathway play an important role in the immune response to tumors. We describe here that the overexpression of PSMB8 and PSMB9, two components of the immunoproteasome, is predictive of better survival and improved response to immune-checkpoint inhibitors of melanoma patients. We study the mechanism that underlies this connection by analyzing the antigenic peptide repertoire of cells that overexpress these subunits using HLA peptidomics. We find a higher response of patient-matched tumor infiltrating lymphocytes against antigens deferentially presented after immunoproteasome overexpression. which may explain the higher immune infiltration observed in patients with high immunoproteasome expression levels. Importantly, we find that PSMB8 and PSMB9 expression levels are much stronger predictors of melanoma patients immune response to checkpoint inhibitors than the tumors mutational burden. Taken together, these results suggest that their expression levels can serve as important biomarkers for stratifying melanoma patients for immune-checkpoint treatment.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Melanocyte, Cell Culture

DISEASE(S): Melanoma

SUBMITTER: Shelly Kalaora  

LAB HEAD: Yardena Samuels

PROVIDER: PXD015957 | Pride | 2020-02-18

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
108T_EV1.raw Raw
108T_EV2.raw Raw
108T_EV3.raw Raw
108T_IFN1.raw Raw
108T_IFN2.raw Raw
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Publications


Predicting the outcome of immunotherapy treatment in melanoma patients is challenging. Alterations in genes involved in antigen presentation and the interferon gamma (IFNγ) pathway play an important role in the immune response to tumors. We describe here that the overexpression of PSMB8 and PSMB9, two major components of the immunoproteasome, is predictive of better survival and improved response to immune-checkpoint inhibitors of melanoma patients. We study the mechanism underlying this connect  ...[more]

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