T-Regulatory Cells: Key Players in Tumor Immune Escape and Angiogenesis
TLDR
The ways in which Tregs suppress the antitumor immune response are discussed and elaborate on the recent discovery that T Regs make significant direct contributions to tumor angiogenesis.Abstract:
T-regulatory cells (Tregs) are found infiltrating tumors in a vast array of tumor types, and tumor-infiltrating Tregs are often associated with a poor clinical outcome. Tregs are potent immunosuppressive cells of the immune system that promote progression of cancer through their ability to limit antitumor immunity and promote angiogenesis. Here, we discuss the ways in which Tregs suppress the antitumor immune response and elaborate on our recent discovery that Tregs make significant direct contributions to tumor angiogenesis. Further, we highlight several current therapies aimed at eliminating Tregs in cancer patients. Given the multifaceted role of Tregs in cancer, a greater understanding of their functions will ultimately strengthen future therapies.read more
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Survival, Durable Tumor Remission, and Long-Term Safety in Patients With Advanced Melanoma Receiving Nivolumab
Suzanne L. Topalian,Mario Sznol,David F. McDermott,Harriet M. Kluger,Richard D. Carvajal,William H. Sharfman,Julie R. Brahmer,Donald P. Lawrence,Michael B. Atkins,John D. Powderly,Philip D. Leming,Evan J. Lipson,Igor Puzanov,David Smith,Janis M. Taube,Jon M. Wigginton,Georgia Kollia,Ashok Kumar Gupta,Drew M. Pardoll,Jeffrey A. Sosman,F. Stephen Hodi +20 more
TL;DR: Overall survival following nivolumab treatment in patients with advanced treatment-refractory melanoma compares favorably with that in literature studies of similar patient populations, and responses were durable and persisted after drug discontinuation.
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Eran Elinav,Roni Nowarski,Christoph A. Thaiss,Bo Hu,Chengcheng Jin,Richard A. Flavell,Richard A. Flavell +6 more
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References
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TL;DR: This work has been supported by the Department of the Army and the National Institutes of Health, and the author acknowledges the support and encouragement of the National Cancer Institute.
Journal ArticleDOI
Type, Density, and Location of Immune Cells Within Human Colorectal Tumors Predict Clinical Outcome
Jérôme Galon,Anne Costes,Fátima Sánchez-Cabo,Amos Kirilovsky,Bernhard Mlecnik,Christine Lagorce-Pagès,Marie Tosolini,Matthieu Camus,Anne Berger,Philippe Wind,Franck Zinzindohoué,Patrick Bruneval,Paul-Henri Cugnenc,Zlatko Trajanoski,Wolf H. Fridman,Franck Pagès +15 more
TL;DR: In situ analysis of tumor-infiltrating immune cells may be a valuable prognostic tool in the treatment of colorectal cancer and possibly other malignancies.
Journal ArticleDOI
Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival.
Tyler J. Curiel,George Coukos,Linhua Zou,Xavier Alvarez,Pui Cheng,Peter Mottram,Melina Evdemon-Hogan,Jose R. Conejo-Garcia,Lin Zhang,Matthew E. Burow,Yun Zhu,Shuang Wei,Ilona Kryczek,Ben Daniel,Alan N. Gordon,Leann Myers,Andrew A. Lackner,Mary L. Disis,Keith L. Knutson,Lieping Chen,Weiping Zou +20 more
TL;DR: It is shown, in detailed studies of CD4+CD25+FOXP3+ Treg cells in 104 individuals affected with ovarian carcinoma, that human tumor T Reg cells suppress tumor-specific T cell immunity and contribute to growth of human tumors in vivo.
Journal ArticleDOI
Conversion of Peripheral CD4+CD25− Naive T Cells to CD4+CD25+ Regulatory T Cells by TGF-β Induction of Transcription Factor Foxp3
Wanjun Chen,Wenwen Jin,Neil J. Hardegen,Ke Jian Lei,Li Li,Nancy J. Marinos,George McGrady,Sharon M. Wahl +7 more
TL;DR: Novel evidence is presented that conversion of naive peripheral CD4+CD25− T cells into anergic/suppressor cells that are CD25+, CD45RB−/low and intracellular CTLA-4+ can be achieved through costimulation with T cell receptors (TCRs) and transforming growth factor β (TGF-β).
Journal ArticleDOI
Ipilimumab plus Dacarbazine for Previously Untreated Metastatic Melanoma
Caroline Robert,Luc Thomas,Igor Bondarenko,Steven J. O'Day,Jeffrey S. Weber,Claus Garbe,Céleste Lebbé,Jean Francois Baurain,Alessandro Testori,Jean-Jacques Grob,Neville Davidson,Jon M. Richards,Michele Maio,Axel Hauschild,Wilson H. Miller,Pere Gascón,Michal Lotem,Kaan Harmankaya,Ramy Ibrahim,Stephen Francis,Tai-Tsang Chen,R. Humphrey,Axel Hoos,Jedd D. Wolchok +23 more
TL;DR: Ipilimumab (at a dose of 10 mg per kilogram) in combination with dacarbazine, as compared with dACarbazine plus placebo, improved overall survival in patients with previously untreated metastatic melanoma.
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