MassIVE MSV000098579

Partial Public PXD066359

ERBB2 signaling drives immune cell evasion and resistance against immunotherapy in small cell lung cancer

Subscribe Comment Add Reanalysis

Description

Small cell lung cancer (SCLC) represents ~15% of all lung cancers and is characterized by its highly aggressive phenotype and its dismal outcome. Though the addition of immune checkpoint blockade to carboplatin and etoposide treatment has improved outcome in SCLC patients, SCLC cells finally acquire the ability to evade immunosurveillance and resistance against immune checkpoint blockade. To elaborate molecular mechanisms that mediate SCLC immune evasion, we performed high dimensional profiling of human and murine SCLC specimens. We herein comprehensively analyzed matched human samples of primary and metastatic SCLC and found a loss of MHC-I in SCLC metastases indicating that MHC-I loss mediates SCLC immune evasion. Silencing MHC-I in SCLC cells drastically diminished immune cell infiltration and facilitated the formation of metastasis in mice by circumventing immune surveillance. Using mass spectrometry and phospho-tyrosine kinase analysis, we discovered that ERBB2 signaling suppresses MHC-I expression in SCLC cells and stimulates immune modulating transcripts. Mechanistically, genetic and/or pharmacologic blockade of the ERBB2 signaling axis was sufficient to induce MHC-I expression and to prevent immune evasion in autochthonous murine SCLC in a STING-dependent manner. Finally, we demonstrate that the ERBB2 signaling axis regulates MHC-I expression on SCLC cells and is critical in maintaining immune evasion in SCLC. Most strikingly, we here uncover synergistic treatment efficacy by combining ERBB2 inhibition with PD-1 blockade eliciting profound responses in preclinical SCLC models and circumventing MHC-I loss under immunotherapy, suggesting this combination for future clinical trials in patients with SCLC. [doi:10.25345/C5XW48846] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: ERBB2 ; DatasetType:Proteomics

Contact

Principal Investigators:
(in alphabetical order) 		Roland Ullrich, University cologne, Germany
Submitting User: BHaeup

Publications

Meder L, Orschel CI, Bouchez CL, Gholamipoorfard R, Orschel CV, Stahl D, Kreer C, Koker M, Nill M, Kocak IG, Noh KW, Zhao X, Ullrich L, Häupl B, Jakob J, Eich ML, Florin A, Grüll H, Wolf J, Beleggia F, Büttner R, Oellerich T, Klein F, Brägelmann J, Reinhardt HC, Abedpour N, Ullrich RT.
ERBB2 signaling drives immune cell evasion and resistance against immunotherapy in small cell lung cancer.
Nat Commun. 2025 Dec 9;16(1):10983. Epub 2025 Dec 9.

Number of Files:
Total Size:
Spectra:
Subscribers:
 
Owner Reanalyses
Experimental Design
    Conditions:
    Biological Replicates:
    Technical Replicates:
 
Identification Results
    Proteins (Human, Remapped):
    Proteins (Reported):
    Peptides:
    Variant Peptides:
    PSMs:
 
Quantification Results
    Differential Proteins:
    Quantified Proteins:
 
Browse Dataset Files
 
FTP Download Link (click to copy):

Species

Instrument

Modifications

- Dataset Reanalyses

+ Dataset History

Click here to queue conversion of this dataset's submitted spectrum files to open formats (e.g. mzML). This process may take some time.

When complete, the converted files will be available in the "ccms_peak" subdirectory of the dataset's FTP space (accessible via the "FTP Download" link to the right).
Number of distinct conditions across all analyses (original submission and reanalyses) associated with this dataset.

Distinct condition labels are counted across all files submitted in the "Metadata" category having a "Condition" column in this dataset.

"N/A" means no results of this type were submitted.
Number of distinct biological replicates across all analyses (original submission and reanalyses) associated with this dataset.

Distinct replicate labels are counted across all files submitted in the "Metadata" category having a "BioReplicate" or "Replicate" column in this dataset.

"N/A" means no results of this type were submitted.
Number of distinct technical replicates across all analyses (original submission and reanalyses) associated with this dataset.

The technical replicate count is defined as the maximum number of times any one distinct combination of condition and biological replicate was analyzed across all files submitted in the "Metadata" category. In the case of fractionated experiments, only the first fraction is considered.

"N/A" means no results of this type were submitted.
Originally identified proteins that were automatically remapped by MassIVE to proteins in the SwissProt human reference database.

"N/A" means no results of this type were submitted.
Number of distinct protein accessions reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Number of distinct unmodified peptide sequences reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Number of distinct peptide sequences (including modified variants or peptidoforms) reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Total number of peptide-spectrum matches (i.e. spectrum identifications) reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Number of distinct proteins quantified across all analyses (original submission and reanalyses) associated with this dataset.

Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

"N/A" means no results of this type were submitted.
Number of distinct proteins found to be differentially abundant in at least one comparison across all analyses (original submission and reanalyses) associated with this dataset.

A protein is differentially abundant if its change in abundance across conditions is found to be statistically significant with an adjusted p-value <= 0.05 and lists no issues associated with statistical tests for differential abundance.

Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

"N/A" means no results of this type were submitted.
This dataset may not contain all raw spectra data as originally deposited in PRIDE. It has been imported to MassIVE for reanalysis purposes, so its spectra data here may consist solely of processed peak lists suitable for reanalysis with most software.