PXD029489

PXD029489 is an original dataset announced via ProteomeXchange.

Title	RNF31 inhibition sensitizes tumors to bystander killing by innate and adaptive immune cells
Description	Tumor escape mechanisms for immunotherapy include deficiencies in antigen presentation, diminishing adaptive CD8+ T cell antitumor activity. Although innate NK cells are triggered by loss of MHC class I, their response is often inadequate. To increase tumor susceptibility to both innate and adaptive immune elimination, we performed parallel genome-wide CRISPR-Cas9 screens. This identified all components, RNF31, RBCK1, and SHARPIN, of the linear ubiquitination chain assembly complex (LUBAC). Genetic and pharmacologic ablation of RNF31, an E3 ubiquitin ligase, strongly sensitized melanoma, breast and colorectal cancer cells to both NK and CD8+ T cell killing. This occurred in a TNF-dependent manner, causing loss of A20 and non-canonical IKK complexes from TNF Receptor Complex I. Corroborating this preclinically, a small molecule RNF31 inhibitor sensitized human colon carcinoma organoids to TNF and greatly enhanced immune bystander killing of antigen-loss and antigen presentation machinery-deficient tumor cells. These results merit exploration of RNF31 inhibition as a clinical pharmacological opportunity for immunotherapy-refractory cancers.
HostingRepository	PRIDE
AnnounceDate	2022-05-30
AnnouncementXML	Submission_2022-05-30_00:36:22.796.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kelly Stecker
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-11-02 03:53:58	ID requested
⏵ 1	2022-05-30 00:36:23	announced

Dataset with its publication pending

submitter keyword: TNF, RNF31, AP

Maarten Altelaar
contact affiliation	Utrecht University
contact email	m.altelaar@uu.nl
lab head
Kelly Stecker
contact affiliation	Utrecht University
contact email	k.e.stecker@uu.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD029489
     1. Label: PRIDE project
     2. Name: RNF31 inhibition sensitizes tumors to bystander killing by innate and adaptive immune cells