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- W4294104532 abstract "Abstract Interactions between immune and tumor cells are critical to determining cancer progression and response. In addition, preclinical prediction of immune-related drug efficacy is limited by inter-species differences between human and mouse, as well as inter-person germline and somatic variation. Here we develop an autologous system that models the TME in individual patients. With patient-derived bone marrow, we engrafted a patient’s hematopoietic system in MISTRG6 mice followed by patient-derived xenograft (PDX) tissue, providing a genetically matched autologous model. We used this system to prospectively study tumor-immune interactions in solid tumor patients. Autologous PDX mice generated innate and adaptive immune populations; these cells populated the TME; and tumors from autologously engrafted mice grew larger than tumors from non-engrafted littermate controls. Single-cell transcriptomics revealed a prominent VEGF-A signature in TME myeloid cells, and inhibition of human VEGF-A abrogated enhanced growth, demonstrating the utility of the autologous PDX system for pre-clinical testing." @default.
- W4294104532 created "2022-09-01" @default.
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- W4294104532 date "2022-08-19" @default.
- W4294104532 modified "2023-09-27" @default.
- W4294104532 title "Autologous humanized PDX modeling for immuno-oncology recapitulates the human tumor microenvironment" @default.
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- W4294104532 doi "https://doi.org/10.1101/2022.08.19.503502" @default.
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