Reprogramming NK cells and macrophages via combined antibody and cytokine therapy primes tumors for elimination by checkpoint blockade.
Animals
Antibodies
Cell Line, Tumor
Humans
Immune Checkpoint Inhibitors
/ immunology
Immunotherapy
/ methods
Interleukin-2
/ pharmacology
Killer Cells, Natural
/ metabolism
Macrophages
/ immunology
Mice
Mice, Inbred C57BL
Neoplasms
/ drug therapy
Programmed Cell Death 1 Receptor
/ metabolism
Tumor Microenvironment
/ immunology
NK cell
checkpoint blockade
interleukin-2
macrophage
sensitization
tumor microenvironment
tumor-targeting antibody
vascular normalization
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
23 11 2021
23 11 2021
Historique:
received:
26
05
2021
revised:
29
09
2021
accepted:
27
10
2021
entrez:
24
11
2021
pubmed:
25
11
2021
medline:
15
2
2022
Statut:
ppublish
Résumé
Treatments aiming to augment immune checkpoint blockade (ICB) in cancer often focus on T cell immunity, but innate immune cells may have important roles to play. Here, we demonstrate a single-dose combination treatment (termed AIP) using a pan-tumor-targeting antibody surrogate, half-life-extended interleukin-2 (IL-2), and anti-programmed cell death 1 (PD-1), which primes tumors to respond to subsequent ICB and promotes rejection of large established tumors in mice. Natural killer (NK) cells and macrophages activated by AIP treatment underwent transcriptional reprogramming; rapidly killed cancer cells; governed the recruitment of cross-presenting dendritic cells (DCs) and other leukocytes; and induced normalization of the tumor vasculature, facilitating further immune infiltration. Thus, innate cell-activating therapies can initiate critical steps leading to a self-sustaining cycle of T cell priming driven by ICB.
Identifiants
pubmed: 34818534
pii: S2211-1247(21)01503-5
doi: 10.1016/j.celrep.2021.110021
pmc: PMC8653865
mid: NIHMS1759310
pii:
doi:
Substances chimiques
Antibodies
0
Immune Checkpoint Inhibitors
0
Interleukin-2
0
Programmed Cell Death 1 Receptor
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
Pagination
110021Subventions
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA014051
Pays : United States
Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests D.J.I. and C.W. are named as inventors on a patent application filed by MIT for 1X AIP therapy.
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