Journal ArticleDOI
Translating gammadelta (γδ) T cells and their receptors into cancer cell therapies
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TLDR
The challenges and opportunities for the clinical implementation of cancer immunotherapies based on γδT cells and their receptors are discussed, which display potent cytotoxicity towards a large array of haematological and solid tumours while preserving normal tissues.Abstract:
Clinical responses to checkpoint inhibitors used for cancer immunotherapy seemingly require the presence of αβT cells that recognize tumour neoantigens, and are therefore primarily restricted to tumours with high mutational load. Approaches that could address this limitation by engineering αβT cells, such as chimeric antigen receptor T (CAR T) cells, are being investigated intensively, but these approaches have other issues, such as a scarcity of appropriate targets for CAR T cells in solid tumours. Consequently, there is renewed interest among translational researchers and commercial partners in the therapeutic use of γδT cells and their receptors. Overall, γδT cells display potent cytotoxicity, which usually does not depend on tumour-associated (neo)antigens, towards a large array of haematological and solid tumours, while preserving normal tissues. However, the precise mechanisms of tumour-specific γδT cells, as well as the mechanisms for self-recognition, remain poorly understood. In this Review, we discuss the challenges and opportunities for the clinical implementation of cancer immunotherapies based on γδT cells and their receptors.read more
Citations
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Cancer immunotherapy with γδ T cells: many paths ahead of us
TL;DR: Recent developments to enhance the efficacy of γδ T cell-based immunotherapy are discussed, including strategies for in vivo activation and tumor-targeting of δ T cells, the optimization of in vitro expansion protocols, and the development of gene-modified γ Δ T cells.
Journal ArticleDOI
γδ T cells in tissue physiology and surveillance.
TL;DR: The roles of γδ T cells in tissue homeostasis and in surveillance of infection are reviewed, aiming to illustrate their major impact on tissue integrity, tissue repair and immune protection.
Journal ArticleDOI
Immunobiology and immunotherapy of HCC: spotlight on innate and innate-like immune cells
TL;DR: The role of innate and innate-like immune cells in liver cancer is highlighted and strategies to therapeutically target them are proposed and current immunotherapeutic strategies in HCC are discussed.
Journal ArticleDOI
Allogeneic Vγ9Vδ2 T-cell immunotherapy exhibits promising clinical safety and prolongs the survival of patients with late-stage lung or liver cancer.
Yan Xu,Zheng Xiang,Mohammed Alnaggar,Mohammed Alnaggar,Léonce Kouakanou,Jiawei Li,Junyi He,Jiashuang Yang,Yi Hu,Yan Chen,Li Lin,Jianlei Hao,Jingxia Li,Jibing Chen,Man Li,Qingling Wu,Christian Peters,Qinghua Zhou,Jianshuang Li,Yingqing Liang,Xiaohua Wang,Baohui Han,Meili Ma,Dieter Kabelitz,Kecheng Xu,Wenwei Tu,Yangzhe Wu,Zhinan Yin +27 more
TL;DR: A novel formula to improve the expansion of peripheral γδ T cells from healthy donors was developed and it was found that the expanded cells possessed significantly improved immune effector functions, including proliferation, differentiation, and cancer cell killing, both in vitro and in the humanized mouse model.
References
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Journal ArticleDOI
Genetic Basis for Clinical Response to CTLA-4 Blockade in Melanoma
Alexandra Snyder,Vladimir Makarov,Taha Merghoub,Jianda Yuan,Jesse M. Zaretsky,Alexis Desrichard,Logan A. Walsh,Michael A. Postow,Phillip Wong,Teresa S. Ho,Travis J. Hollmann,Cameron Bruggeman,Kasthuri Kannan,Yanyun Li,Ceyhan Elipenahli,Cailian Liu,Christopher T. Harbison,Lisu Wang,Antoni Ribas,Jedd D. Wolchok,Jedd D. Wolchok,Timothy A. Chan +21 more
TL;DR: In this paper, the authors provide clarification and correction to their article "Genetic Basis for Clinical Response to CTLA-4 Blockade in Melanoma" (Dec. 4, 2014, issue).
Correction: Genetic Basis for Clinical Response to CTLA-4 Blockade in Melanoma
Timothy A. Chan,Jedd D. Wolchok +1 more
TL;DR: These findings define a genetic basis for benefit from CTLA-4 blockade in melanoma and provide a rationale for examining exomes of patients for whom anti-CTLA- 4 agents are being considered.
Journal ArticleDOI
The prognostic landscape of genes and infiltrating immune cells across human cancers
Andrew J. Gentles,Aaron M. Newman,Chih Long Liu,Scott V. Bratman,Scott V. Bratman,Weiguo Feng,Dongkyoon Kim,Viswam S. Nair,Yue Xu,Amanda Khuong,Chuong D. Hoang,Maximilian Diehn,Robert B. West,Sylvia K. Plevritis,Ash A. Alizadeh +14 more
TL;DR: A pan-cancer resource and meta-analysis of expression signatures from ∼18,000 human tumors with overall survival outcomes across 39 malignancies is presented and it is found that expression of favorably prognostic genes, including KLRB1 (encoding CD161), largely reflect tumor-associated leukocytes.
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