ArticleCancer discovery2024
Receptor-interacting Protein Kinase 2 Is an Immunotherapy Target in Pancreatic Cancer.
Article in Cancer discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Macrophage-associated kinase signaling in atherosclerosis - a systematic review.Cell communication and signaling : CCS · 2026Pooled it
- Autophagy modulation in cancer.Nature reviews. Drug discovery · 2026Review
- Nanomaterial-driven spatiotemporal autophagy modulation: The dual-edged sword in precision cancer therapy.Acta pharmaceutica Sinica. B · 2026Review
- Targeting DGAT1 reprograms lipid landscape and restores CD8⁺ T cell immunity in pancreatic cancer.Nature communications · 2026Article
- Ripk2 promotes CD8Cell death & disease · 2026Article
- Tumor sialylation regulates G-CSF stability and promotes neutrophil-mediated immunosuppression in breast cancer.Nature communications · 2026Article
- Targeting the OTU family: a core therapeutic strategy for reshaping the immunosuppressive microenvironment and reversing drug resistance in HCC by coordinating the autophagy-ferroptosis balance.Cell death discovery · 2026Review
- The degradation revolution: harnessing targeted protein degradation for the treatment of human diseases.Cellular and molecular life sciences : CMLS · 2026Review
- Review
- ULK1 drives NDP52-mediated selective autophagic degradation of MHC-I to promote immune evasion in HPV-positive head and neck cancer.bioRxiv : the preprint server for biology · 2026Article
- Construction of a SEMA3 family-based model to predict prognosis and molecular subtypes in pancreatic ductal adenocarcinoma.Discover oncology · 2026Article
- Mature tertiary lymphoid structures tumor microenvironment-based risk model to assess patients with pancreatic ductal adenocarcinoma.Translational cancer research · 2026Article
- CRISPR screening redefines therapeutic target identification and drug discovery with precision and scalability.Journal of pharmaceutical analysis · 2026Review
- Multifunctional extracellular vesicles inhibiting autophagy ameliorate immunotherapy in non-small cell lung cancer.Acta pharmaceutica Sinica. B · 2026Article
- Cathepsin-D-mediated MHC class I degradation contributes to immune evasion in colorectal cancer.Cell reports. Medicine · 2026Article
- RIPK2 induces docetaxel resistance in prostate cancer through the NF-κB/P-gp signaling pathway.PloS one · 2026Article
- High-throughput screening to engineer optimal T cell therapies: current knowledge and future prospects.Frontiers in oncology · 2026Review
- Stimulator of interferon genes signaling network-driven prognostic signature for pancreatic cancer: Hub gene discovery with multimodal validation.Oncology letters · 2025Article
- Autophagy-Targeting Fe-Cu Nanozyme for Tumor Immune Microenvironment Remodeling and Image-Guided Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Epigenetic suppression of Nrf2-Slc40a1 axis induces ferroptosis and enhances immunotherapy in pancreatic cancer.Journal for immunotherapy of cancer · 2025Article
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Authors and funding
16 authors at 5 institutions in 1 country.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy because of its aggressive nature and the paucity of effective treatment options. Almost all registered drugs have proven ineffective in addressing the needs of patients with PDAC. This is the result of a poor understanding of the unique tumor-immune microenvironment (TME) in PDAC. To identify druggable regulators of immunosuppressive TME, we performed a kinome- and membranome-focused CRISPR screening using orthotopic PDAC models. Our data showed that receptor-interacting protein kinase 2 (RIPK2) is a crucial driver of immune evasion of cytotoxic T-cell killing and that genetic or pharmacologic targeting of RIPK2 sensitizes PDAC to anti-programmed cell death protein 1 (anti-PD-1) immunotherapy, leading to prolonged survival or complete regression. Mechanistic studies revealed that tumor-intrinsic RIPK2 ablation disrupts desmoplastic TME and restores MHC class I (MHC-I) surface levels through eliminating NBR1-mediated autophagy-lysosomal degradation. Our results provide a rationale for a novel combination therapy consisting of RIPK2 inhibition and anti-PD-1 immunotherapy for PDAC. SIGNIFICANCE: PDAC is resistant to almost all available therapies, including immune checkpoint blockade. Through in vivo CRISPR screen, we identified that RIPK2 plays a crucial role in facilitating immune evasion by impeding antigen presentation and cytotoxic T-cell killing. Targeting tumor-intrinsic RIPK2 either genetically or pharmacologically improves PDAC to anti-PD-1 immunotherapy. See related commentary by Liu et al., p. 208 . This article is featured in Selected Articles from This Issue, p. 201.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.