Plasma fractalkine contributes to systemic myeloid diversity and PD-L1/PD-1 blockade in lung cancer.
NK cells
adenocarcinoma
biomarker
monocytes
neutrophils
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
03 08 2023
03 08 2023
Historique:
revised:
17
05
2023
received:
01
08
2022
accepted:
02
06
2023
medline:
4
8
2023
pubmed:
27
6
2023
entrez:
27
6
2023
Statut:
ppublish
Résumé
Recent studies highlight the importance of baseline functional immunity for immune checkpoint blockade therapies. High-dimensional systemic immune profiling is performed in a cohort of non-small-cell lung cancer patients undergoing PD-L1/PD-1 blockade immunotherapy. Responders show high baseline myeloid phenotypic diversity in peripheral blood. To quantify it, we define a diversity index as a potential biomarker of response. This parameter correlates with elevated activated monocytic cells and decreased granulocytic phenotypes. High-throughput profiling of soluble factors in plasma identifies fractalkine (FKN), a chemokine involved in immune chemotaxis and adhesion, as a biomarker of response to immunotherapy that also correlates with myeloid cell diversity in human patients and murine models. Secreted FKN inhibits lung adenocarcinoma growth in vivo through a prominent contribution of systemic effector NK cells and increased tumor immune infiltration. FKN sensitizes murine lung cancer models refractory to anti-PD-1 treatment to immune checkpoint blockade immunotherapy. Importantly, recombinant FKN and tumor-expressed FKN are efficacious in delaying tumor growth in vivo locally and systemically, indicating a potential therapeutic use of FKN in combination with immunotherapy.
Identifiants
pubmed: 37366231
doi: 10.15252/embr.202255884
pmc: PMC10398648
doi:
Substances chimiques
B7-H1 Antigen
0
Biomarkers
0
Chemokine CX3CL1
0
CX3CL1 protein, human
0
Cx3cl1 protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e55884Informations de copyright
© 2023 The Authors. Published under the terms of the CC BY 4.0 license.
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