ArticleJournal of immunology (Baltimore, Md. : 1950)2018
Tumor Tolerance-Promoting Function of Regulatory T Cells Is Optimized by CD28, but Strictly Dependent on Calcineurin.
Article in Journal of immunology (Baltimore, Md. : 1950), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Mathematical and Mouse Models Identify Regulatory T Cell Influx as A Key Determinant of Acquired Resistance to PD-1 Immunotherapy.Cancer research · 2026Article
- Chemokines that govern T cell activity in tumors.Current opinion in immunology · 2025Review
- Infiltrating treg reprogramming in the tumor immune microenvironment and its optimization for immunotherapy.Biomarker research · 2024Review
- Interruption of the intratumor CD8Cancer cell · 2024Article
- PD-1 or CTLA-4 blockade promotes CD86-driven Treg responses upon radiotherapy of lymphocyte-depleted cancer in mice.The Journal of clinical investigation · 2024Article
- Construction of an immune-related risk score signature for gastric cancer based on multi-omics data.Scientific reports · 2024Article
- CTLA-4 Checkpoint Inhibition Improves Sepsis Survival in Alcohol-Exposed Mice.ImmunoHorizons · 2024Article
- How chemokines organize the tumour microenvironment.Nature reviews. Cancer · 2024Review
- Diversity of intratumoral regulatory T cells in B-cell non-Hodgkin lymphoma.Blood advances · 2023Article
- PD-1 and CTLA-4 exert additive control of effector regulatory T cells at homeostasis.Frontiers in immunology · 2023Article
- Expansion of tumor-associated Treg cells upon disruption of a CTLA-4-dependent feedback loop.Cell · 2021Article
- Therapeutic Targets and Tumor Microenvironment in Colorectal Cancer.Journal of clinical medicine · 2021Review
- Bcl10 is required for the development and suppressive function of Foxp3Cellular & molecular immunology · 2021Article
- Latest Advances in Targeting the Tumor Microenvironment for Tumor Suppression.International journal of molecular sciences · 2019Review
- Treg programming and therapeutic reprogramming in cancer.Immunology · 2019Review
- Guidance factors orchestrating regulatory T cell positioning in tissues during development, homeostasis, and response.Immunological reviews · 2019Review
- Tissue resident and follicular Treg cell differentiation is regulated by CRAC channels.Nature communications · 2019Article
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Authors and funding
11 authors.
Funding
Abstract
Regulatory T cells (Treg) restrain immune responses against malignant tumors, but their global depletion in cancer patients will likely be limited by systemic autoimmune toxicity. Instead, approaches to "tune" their activities may allow for preferential targeting of tumor-reactive Treg. Although Ag recognition regulates Treg function, the roles of individual TCR-dependent signaling pathways in enabling Treg to promote tumor tolerance are not well characterized. In this study, we examined in mouse tumor models the role of calcineurin, a key mediator of TCR signaling, and the role of the costimulatory receptor CD28 in the differentiation of resting central Treg into effector Treg endowed with tumor tropism. We find that calcineurin, although largely dispensable for suppressive activity in vitro, is essential for upregulation of ICOS and CTLA-4 in Treg, as well as for expression of chemokine receptors driving their accumulation in tumors. In contrast, CD28 is not critical, but optimizes the formation of tumor-homing Treg and their fitness in tumor tissue. Accordingly, although deletion of either CnB or CD28 strongly impairs Treg-mediated tumor tolerance, lack of CnB has an even more pronounced impact than lack of CD28. Hence, our studies reveal distinct roles for what has classically been defined as signal 1 and signal 2 of conventional T cell activation in the context of Treg-mediated tumor tolerance.
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