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NSCLC Lung Adenocarcinoma Proteomics

ABSTRACT: Alterations in cellular antigen processing and presenting machinery has gained increased interest as a hallmark of cancer-related inflammation. Growing evidence suggest that proteasome composition and immunoproteasome expression can influence the efficacy of cancer therapies. By applying proteasome foot-printing to clinical samples of Non Small Cell lung Cancer (NSCLC), we found tumor specific alterations in degradation products and increased expression of the proteasome regulator, PA200. We show that increased levels of PA200 alter the cleavage specificities of proteasomal-cleaved peptides and reduce antigenicity. We found that smoking-induced expression of PA200 abrogated immunoproteasome activity and is associated with poor survival. As immunotherapy is becoming a common treatment of NSCLC, we hypothesized that PA200 expression may contribute to resistance mechanism to immunotherapy. Consistent with this possibility, we found that the ratio between PA200 and the immunoproteasome subunit PSMB10, and not their absolute levels, were significantly associated with poor response to Durvalamab. Induced reduction in PA200 in vivo was associated with increased immune infiltration and attenuated tumor growth.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Lung, Epithelial Cell

DISEASE(S): Lung Adenocarcinoma

SUBMITTER: Aaron Javitt

LAB HEAD: Yifat Merbl

PROVIDER: PXD019573 | Pride | 2023-03-30

REPOSITORIES: Pride

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