| Autor: |
Bryan M. Burt, Farrah Kheradmand, Duy T. Le, George Van Buren, Rana Nikzad, Silke Paust, Shawn Abeynaike, Cristina Zalfa |
| Rok vydání: |
2020 |
| Předmět: |
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| Popis: |
Existing patient-derived-xenograft (PDX) mouse models of solid tumors lack a fully tumor-donor matched “syngeneic” and functional immune system. We developed such a model by engrafting lymphopenic recipient mice with a fresh undisrupted piece of solid tumor, whereby tumor-infiltrating lymphocytes (TIL) expanded in the recipient mice for several weeks. Tumors engrafted in about seventy to eighty percent of syngeneic-immune-system-PDX (SIS-PDX) mice, which harbored tumor-exhausted immune-effector and functional immune-regulatory cells persisting for at least six-months post-engraftment. Interleukin-15 (IL-15)-stimulation in addition to immune checkpoint inhibition (ICI), prevented resistance, resulting in complete or partial response to combined treatment. Further, the depletion of Cytotoxic T lymphocytes (CTLs) and/or Natural Killer (NK) cells from combined immunotherapy in SIS-PDX mice revealed that both cell types are required for the maximal response to tumor. Our novel SIS-PDX model provides a valuable resource for powerful mechanistic and therapeutic studies designed to eradicate solid tumors. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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