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- Chrystal M. Paulos
- Authors' Affiliation: National Cancer Institute, NIH, Bethesda, Maryland
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- Andrew Kaiser
- Authors' Affiliation: National Cancer Institute, NIH, Bethesda, Maryland
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- Claudia Wrzesinski
- Authors' Affiliation: National Cancer Institute, NIH, Bethesda, Maryland
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- Christian S. Hinrichs
- Authors' Affiliation: National Cancer Institute, NIH, Bethesda, Maryland
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- Lydie Cassard
- Authors' Affiliation: National Cancer Institute, NIH, Bethesda, Maryland
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- Andrea Boni
- Authors' Affiliation: National Cancer Institute, NIH, Bethesda, Maryland
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- Pawel Muranski
- Authors' Affiliation: National Cancer Institute, NIH, Bethesda, Maryland
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- Luis Sanchez-Perez
- Authors' Affiliation: National Cancer Institute, NIH, Bethesda, Maryland
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- Douglas C. Palmer
- Authors' Affiliation: National Cancer Institute, NIH, Bethesda, Maryland
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- Zhiya Yu
- Authors' Affiliation: National Cancer Institute, NIH, Bethesda, Maryland
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- Paul A. Antony
- Authors' Affiliation: National Cancer Institute, NIH, Bethesda, Maryland
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- Luca Gattinoni
- Authors' Affiliation: National Cancer Institute, NIH, Bethesda, Maryland
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- Steven A. Rosenberg
- Authors' Affiliation: National Cancer Institute, NIH, Bethesda, Maryland
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- Nicholas P. Restifo
- Authors' Affiliation: National Cancer Institute, NIH, Bethesda, Maryland
説明
<jats:title>Abstract</jats:title><jats:p>Lymphodepletion with chemotherapeutic agents or total body irradiation (TBI) before adoptive transfer of tumor-specific T cells is a critical advancement in the treatment of patients with melanoma. More than 50% of patients that are refractory to other treatments experience an objective or curative response with this approach. Emerging data indicate that the key mechanisms underlying how TBI augments the functions of adoptively transferred T cells include (a) the depletion of regulatory T cells (Treg) and myeloid-derived suppressor cells that limit the function and proliferation of adoptively transferred cells; (b) the removal of immune cells that act as “sinks” for homeostatic cytokines, whose levels increase after lymphodepletion; and (c) the activation of the innate immune system via Toll-like receptor 4 signaling, which is engaged by microbial lipopolysaccharide that translocated across the radiation-injured gut. Here, we review these mechanisms and focus on the effect of Toll-like receptor agonists in adoptive immunotherapy. We also discuss alternate regimens to chemotherapy or TBI, which might be used to safely treat patients with advanced disease and promote tumor regression.</jats:p>
収録刊行物
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- Clinical Cancer Research
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Clinical Cancer Research 13 (18), 5280-5289, 2007-09-15
American Association for Cancer Research (AACR)
