New ProteomeXchange dataset PXD060523

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https://proteomecentral.proteomexchange.org/dataset/PXD060523

Summary of dataset

Status: new
Identifier: PXD060523
HostingRepository: PRIDE
Species: Mus musculus
Title: Essential role of NLRC5 in cancer immune surveillance and cancer immunoediting
Submitter: Jean-Francois Lucier
LabHead: Subburaj Ilangumaran
Description: Background/Objectives: Downregulation of NLRC5, the transcriptional activator of MHC class-I, results in tumor immune evasion via escape from CD8+ T cell-mediated tumor control. As NLRC5 deficiency does not abrogate CD8+ T cell development, we investigated whether NLRC5-dependent antitumor immune mechanisms are required for immune surveillance. Methods: Development of 3-methylcholanthrene (MCA)-induced endogenous fibrosarcoma was studied in Nlrc5-/- mice with Nlrc5+/+ and Rag1-/- mice serving as controls. Tumors were histologically examined. Tumor cell lines established from MCA-induced tumors were evaluated for their sensitivity to immune-mediated growth control following implantation into immunocompetent C57BL/6 and immunodeficient Rag1-/- hosts. Proteomes of MCA-induced tumors were analysed by mass spectrometry followed by pathway analysis. Results: Nlrc5-/- and Rag1-/- mice showed increased propensity to develop MCA-induced tumors with elevated growth rate compared t
o Nlrc5+/+ mice, and displayed significantly reduced survival. Tumors from Nlrc5+/+ and Nlrc5-/- mice, but not from Rag1-/- mice, contained necrotic areas and displayed T cell infiltration. Tumors formed by Nlrc5+/+ tumor cell lines progressed unhindered in C57BL/6 hosts that reflected their immunoedited status, whereas cell lines from Nlrc5-/- and Rag1-/- tumors were efficiently controlled, indicating their non-immunoedited status. Proteomic analysis revealed enrichment of granzyme-mediated cytolytic pathway in Nlrc5+/+ tumors that were absent in Nlrc5-/- tumors, which showed enrichment of humoral and innate immune pathways. Conclusions: Our data show that NLRC5 is required for robust tumor immune surveillance and tumor immunoediting. Compensatory humoral and innate immune mechanisms activated by the loss of NLRC5 are insufficient for cancer immune surveillance and cancer immunoediting.

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