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Can I read Systematic elucidation and pharmacological targeting of tumor-infiltrating regulatory T cell master regulators on EtoBox?
Systematic elucidation and pharmacological targeting of tumor-infiltrating regulatory T cell master regulators by Aleksandar Obradovic; Casey Ager; Mikko Turunen; Thomas Nirschl; Mohsen Khosravi-Maharlooei; Alina Iuga; Christopher M. Jackson; Srinivasan Yegnasubramanian; Lorenzo Tomassoni; Ester Calvo Fernandez; Patrick McCann; Meri Rogava; Angelo M. DeMarzo; Christina M. Kochel; Mohamad Allaf; Trinity Bivalacqua; Michael Lim; Ronald Realubit; Charles Karan; Charles G. Drake; Andrea Califano is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.
What is Systematic elucidation and pharmacological targeting of tumor-infiltrating regulatory T cell master regulators about?
Due to their immunosuppressive role, tumor-infiltrating regulatory T cells (TI-Tregs) represent attractive immuno-oncology targets. Analysis of TI vs. peripheral Tregs (P-Tregs) from 36 patients, across four malignancies, identified 17 candidate master regulators (MRs) as mechanistic determinants of TI-Treg transcriptional state. Pooled CRISPR-Cas9 screening in vivo, using a chimeric hematopoietic stem cell transplant model, confirmed the essentiality of eight MRs in TI-Treg recruitment and/or retention without affecting other T cell subtypes, and targeting one of the most significant MRs (Trps1) by CRISPR KO significantly reduced ectopic tumor growth. Analysis of drugs capable of inverting TI-Treg MR activity identified low-dose gemcitabine as the top prediction. Indeed, gemcitabine treatment inhibited tumor growth in immunocompetent but not immunocompromised allografts, increased anti-PD-1 efficacy, and depleted MR-expressing TI-Tregs in vivo. This study provides key insight into Treg signaling, specifically in the context of cancer, and a generalizable strategy to systematically elucidate and target MR proteins in immunosuppressive subpopulations.
Who reads Systematic elucidation and pharmacological targeting of tumor-infiltrating regulatory T cell master regulators?
It is typically read by researchers, students, and practitioners in Biochemistry, Genetics and Molecular Biology.
- Author
- Aleksandar Obradovic; Casey Ager; Mikko Turunen; Thomas Nirschl; Mohsen Khosravi-Maharlooei; Alina Iuga; Christopher M. Jackson; Srinivasan Yegnasubramanian; Lorenzo Tomassoni; Ester Calvo Fernandez; Patrick McCann; Meri Rogava; Angelo M. DeMarzo; Christina M. Kochel; Mohamad Allaf; Trinity Bivalacqua; Michael Lim; Ronald Realubit; Charles Karan; Charles G. Drake; Andrea Califano
- Publisher
- Elsevier BV
- Published
- 2023
- Language
- EN
- Field
- Biochemistry, Genetics and Molecular Biology (Life Sciences)