Natural killer cells and cytotoxic T lymphocytes are required to clear solid tumor in a patient-derived xenograft.
Adjuvants, Immunologic
/ pharmacology
Animals
Disease Models, Animal
Heterografts
/ immunology
Humans
Immune Checkpoint Inhibitors
/ pharmacology
Immunotherapy
/ methods
Interleukin-15
/ metabolism
Killer Cells, Natural
/ immunology
Mice
Neoplasm Transplantation
/ immunology
Neoplasms
/ immunology
T-Lymphocytes, Cytotoxic
/ immunology
Transplantation, Heterologous
/ methods
Xenograft Model Antitumor Assays
/ methods
Cancer immunotherapy
Immunology
NK cells
T cells
Journal
JCI insight
ISSN: 2379-3708
Titre abrégé: JCI Insight
Pays: United States
ID NLM: 101676073
Informations de publication
Date de publication:
08 07 2021
08 07 2021
Historique:
pubmed:
4
6
2021
medline:
12
2
2022
entrez:
3
6
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34081628
pii: e140116
doi: 10.1172/jci.insight.140116
pmc: PMC8410059
doi:
pii:
Substances chimiques
Adjuvants, Immunologic
0
Immune Checkpoint Inhibitors
0
Interleukin-15
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCATS NIH HHS
ID : KL2 TR002552
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002550
Pays : United States
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