ArticleScientific reports2021
SHP2 blockade enhances anti-tumor immunity via tumor cell intrinsic and extrinsic mechanisms.
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Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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43citing papers in PubMed
4.6field-weighted citation impact, top 4% of its field
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Who cites it
43 citing papers in PubMed, 72 citations in OpenAlex.
- Nano-Enabled Systemic Delivery of STING Agonist by Engineered Silicasome for Potent Antitumor Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A first-in-human phase 1 study of the SHP2 inhibitor BBP-398 in patients with advanced solid tumors.NPJ precision oncology · 2026Article
- Molecular Mechanisms Driving Metastatic Progression Within the Aged Tumor Microenvironment.International journal of molecular sciences · 2025Review
- SHP2: A Redox-Sensitive Regulator Linking Immune Checkpoint Inhibitor Therapy to Cancer Treatment and Vascular Risk.Antioxidants (Basel, Switzerland) · 2025Review
- RAS Pathway Inhibitors Combined with Targeted Agents Are Active in Patient-Derived Spheroids with Oncogenic KRAS Variants from Multiple Cancer Types.Cancer research communications · 2025Article
- Novel paradigms in KRAS targeting: Unveiling strategies to combat drug resistance.Chinese medical journal · 2025Review
- Targeting SHP2: Dual breakthroughs in colorectal cancer therapy-from signaling pathway modulation to immune microenvironment remodeling.World journal of gastrointestinal oncology · 2025Review
- Pioneer in Molecular Biology: Conformational Ensembles in Molecular Recognition, Allostery, and Cell Function.Journal of molecular biology · 2025Review
- Induced clustering of SHP2-depleted tumor cells in vascular islands restores sensitivity to MEK/ERK inhibition.The Journal of clinical investigation · 2025Article
- The inhibitory receptor Siglec-E controls antigen-presenting cell activation and T cell-mediated transplant rejection.Science translational medicine · 2025Article
- First Results of Migoprotafib, a Potent and Highly Selective Src Homology-2 Domain-Containing Phosphatase 2 Inhibitor in Patients with Advanced Solid Tumors.Molecular cancer therapeutics · 2025Article
- Research into overcoming drug resistance in lung cancer treatment using CRISPR-Cas9 technology: a narrative review.Translational lung cancer research · 2024Review
- Article
- Engineering nanoparticles-enabled tumor-associated macrophages repolarization and phagocytosis restoration for enhanced cancer immunotherapy.Journal of nanobiotechnology · 2024Article
- Splicing neoantigen discovery with SNAF reveals shared targets for cancer immunotherapy.Science translational medicine · 2024Article
- Discovery of 5-Azaquinoxaline Derivatives as Potent and Orally Bioavailable Allosteric SHP2 Inhibitors.ACS medicinal chemistry letters · 2023Article
- Review
- SHP2: A Pleiotropic Target at the Interface of Cancer and Its Microenvironment.Cancer discovery · 2023Review
- SHP2 promotes sarcoidosis severity by inhibiting SKP2-targeted ubiquitination of TBET in CD8Science translational medicine · 2023Article
- PI3K inhibition circumvents resistance to SHP2 blockade in metastatic triple-negative breast cancer.Journal of mammary gland biology and neoplasia · 2023Article
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Authors and funding
48 authors at 2 institutions in 2 countries.
Ye WangOncology Disease Area, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Morvarid MohseniOncology Disease Area, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Angelo GrauelExploratory Immuno-Oncology, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Javier Estrada DiezOncology Disease Area, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Wei GuanExploratory Immuno-Oncology, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Simon LiangOncology Disease Area, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Jiyoung Elizabeth ChoiExploratory Immuno-Oncology, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Minying PuOncology Disease Area, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Dongshu ChenOncology Disease Area, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Tyler LaszewskiExploratory Immuno-Oncology, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Stephanie SchwartzExploratory Immuno-Oncology, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Jane GuOncology Disease Area, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Leandra MansurChemical Biology & Therapeutics, Novartis Institutes for BioMedical Research, Cambridge, USA.
Tyler BurksChemical Biology & Therapeutics, Novartis Institutes for BioMedical Research, Cambridge, USA.
Lauren BrodeurOncology Disease Area, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Roberto VelazquezOncology Disease Area, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Steve KovatsOncology Disease Area, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Bhavesh PantOncology Disease Area, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Giri BuruzulaExploratory Immuno-Oncology, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Emily DengExploratory Immuno-Oncology, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Julie T ChenOncology Disease Area, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Farid Sari-SarrafAnalytical Sciences & Imaging, Novartis Institutes for BioMedical Research, Cambridge, USA.
Christina DornelasAnalytical Sciences & Imaging, Novartis Institutes for BioMedical Research, Cambridge, USA.
Malini VaradarajanOncology Disease Area, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Haiyan YuOncology Disease Area, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Chen LiuOncology Disease Area, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Joanne LimExploratory Immuno-Oncology, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Huai-Xiang HaoOncology Disease Area, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Xiaomo JiangExploratory Immuno-Oncology, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Anthony MalamasOncology Disease Area, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Matthew J LaMarcheGlobal Discovery Chemistry, Novartis Institutes for BioMedical Research, Cambridge, USA.
Felipe Correa GeyerOncology Disease Area, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Margaret McLaughlinOncology Disease Area, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Carlotta CostaOncology Disease Area, Novartis Institutes for BioMedical Research, Basel, Switzerland.
Joel WagnerOncology Disease Area, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
David RuddyOncology Disease Area, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Pushpa JayaramanExploratory Immuno-Oncology, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Nathaniel D KirkpatrickAnalytical Sciences & Imaging, Novartis Institutes for BioMedical Research, Cambridge, USA.
Pu ZhangExploratory Immuno-Oncology, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Oleg IartchoukChemical Biology & Therapeutics, Novartis Institutes for BioMedical Research, Cambridge, USA.
Kimberly AardalenOncology Disease Area, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Viviana CremascoExploratory Immuno-Oncology, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Glenn DranoffExploratory Immuno-Oncology, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Jeffrey A EngelmanOncology Disease Area, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Serena SilverOncology Disease Area, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Hongyun WangOncology Disease Area, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
William D Hastings *Exploratory Immuno-Oncology, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA. bill.hastings@novartis.com.
Silvia Goldoni *Oncology Disease Area, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA. s.goldoni22@gmail.com.
Novartis (United States) · USNovartis (Switzerland) · CH
Funding
No grant is acknowledged in the PubMed record.
Abstract
SHP2 is a ubiquitous tyrosine phosphatase involved in regulating both tumor and immune cell signaling. In this study, we discovered a novel immune modulatory function of SHP2. Targeting this protein with allosteric SHP2 inhibitors promoted anti-tumor immunity, including enhancing T cell cytotoxic function and immune-mediated tumor regression. Knockout of SHP2 using CRISPR/Cas9 gene editing showed that targeting SHP2 in cancer cells contributes to this immune response. Inhibition of SHP2 activity augmented tumor intrinsic IFNγ signaling resulting in enhanced chemoattractant cytokine release and cytotoxic T cell recruitment, as well as increased expression of MHC Class I and PD-L1 on the cancer cell surface. Furthermore, SHP2 inhibition diminished the differentiation and inhibitory function of immune suppressive myeloid cells in the tumor microenvironment. SHP2 inhibition enhanced responses to anti-PD-1 blockade in syngeneic mouse models. Overall, our study reveals novel functions of SHP2 in tumor immunity and proposes that targeting SHP2 is a promising strategy for cancer immunotherapy.
Indexed as
Immunity, CellularAnimalsCell Line, TumorGene Knockout TechniquesHEK293 CellsHumansMiceMice, Inbred BALB CNeoplasm ProteinsNeoplasms, ExperimentalProtein Tyrosine Phosphatase, Non-Receptor Type 11Signal TransductionT-LymphocytesNeoplasm ProteinsProtein Tyrosine Phosphatase, Non-Receptor Type 11PTPN11 protein, humanPtpn11 protein, mouse
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