Journal
JCI INSIGHT
Volume 6, Issue 13, Pages -Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/jci.insight.140116
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Funding
- TSRI
- Barry Stephen Smith Memorial Pancreatic Cancer Research Award from the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine
- Helis Foundation
- National Center for Advancing Translational Sciences, NIH, through Scripps Research Translational Institute [UL1TR002550, KL2TR002552]
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This study developed a novel solid tumor model, where TIL-PDX mice successfully engrafted with fresh solid tumors and harbored tumor-infiltrating lymphocytes, providing a valuable resource for future research.
Existing patient-derived xenograft (PDX) mouse models of solid tumors lack a fully tumor donor-matched, syngeneic, and functional immune system. We developed a model that overcomes these limitations by engrafting lymphopenic recipient mice with a fresh, undisrupted piece of solid tumor, whereby tumor-infiltrating lymphocytes (TILs) persisted in the recipient mice for several weeks. Successful tumor engraftment was achieved in 83% to 89% of TIL-PDX mice, and these were seen to harbor exhausted immuno-effector as well as functional immunoregulatory cells persisting for at least 6 months postengraftment. Combined treatment with interleukin-15 stimulation and immune checkpoint inhibition resulted in complete or partial tumor response in this model. Further, depletion of cytotoxic T lymphocytes and/or natural killer cells before combined immunotherapy revealed that both cell types were required for maximal tumor regression. Our TIL-PDX model provides a valuable resource for powerful mechanistic and therapeutic studies in solid tumors.
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