kozik2020: Small molecule enhancers of endosome-to-cytosol import...

In lgatto/pRolocdata: Data accompanying the pRoloc package

Small molecule enhancers of endosome-to-cytosol import augment anti-tumour immunity

Description

Data from 'Small molecule enhancers of endosome-to-cytosol import augment anti-tumour immunity'

Efficient cross-presentation of antigens by dendritic cells (DCs) is critical for initiation of anti-tumour immune responses. Yet, several steps of antigen intracellular traffic during cross-presentation are incompletely understood: in particular, the molecular mechanisms and the relative importance of antigen import from endocytic compartments into the cytosol. Here, we asked whether antigen import into the cytosol is rate-limiting for cross-presentation and anti-tumour immunity. By screening 700 FDA-approved drugs, we identified 37 import enhancers. We focused on prazosin and tamoxifen, and generated proteomic organellar maps of drug-treated DCs, covering the subcellular localisations of over 2000 proteins. By combining organellar mapping, quantitative proteomics, microscopy, and bioinformatics, we conclude that import enhancers undergo lysosomal trapping leading to membrane permeation and antigen release into the cytosol. Enhancing antigen import facilitates cross-presentation of both soluble and cell-associated antigens. Systemic administration of prazosin also led to reduced growth of MC38 tumours and to a synergistic effect with checkpoint immunotherapy in a melanoma model. Thus, inefficient antigen import into the cytosol limits antigen cross-presentation, restraining the potency of anti-tumour immune responses and efficacy of checkpoint blockers.

Usage

  data("Kozik_con")
  data("Kozik_pra")
  data("Kozik_tam")

Format

The data is an instance of class MSnSet from package MSnbase.

Examples

  data(Kozik_con)
  Kozik_con
  pData(Kozik_con)
  exprs(Kozik_con)[1:3,1:3]
  
  library("pRoloc")
  plot2D(Kozik_con, main = "denderitic cells control")

lgatto/pRolocdata documentation built on Oct. 17, 2024, 10:16 p.m.