The DOI matches its Crossref record; 57 of the 57 references it cites were found in a registry or an index.
Intratumoral Activity of the CXCR3 Chemokine System Is Required for the Efficacy of Anti-PD-1 Therapy
Open accessAbstract
Despite compelling rates of durable clinical responses to programmed cell death-1 (PD-1) blockade, advances are needed to extend these benefits to resistant tumors. We found that tumor-bearing mice deficient in the chemokine receptor CXCR3 responded poorly to anti-PD-1 treatment. CXCR3 and its ligand CXCL9 were critical for a productive CD8+ T cell response in tumor-bearing mice treated with anti-PD-1 but were not required for the infiltration of CD8+ T cells into tumors. The anti-PD-1-induced anti-tumor response was facilitated by CXCL9 production from intratumoral CD103+ dendritic cells, suggesting that CXCR3 facilitates dendritic cell-T cell interactions within the tumor microenvironment. CXCR3 ligands in murine tumors and in plasma of melanoma patients were an indicator of clinical response to anti-PD-1, and their induction in non-responsive murine tumors promoted responsiveness to anti-PD-1. Our data suggest that the CXCR3 chemokine system is a biomarker for sensitivity to PD-1 blockade and that augmenting the intratumoral function of this chemokine system could improve clinical outcomes.
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In the citing paper
“Additionally, CXCL10 has been shown to promote effector T cell generation and function56,57.”
From Epigenetic state determines the in vivo efficacy of STING agonist therapy (2023) · cites this paper as [57]
Experimental — accuracy not yet measuredIn the citing paper
“CXCL9/10/11 are ligands of the CXCR3 receptor involved in increased trafficking of CD8+CXCR3+ T cells to tumors (47,48,64).”
In the citing paper
“The relevance of the CXCL9/10/11-CXCR3 pathway for recruiting and triggering cytotoxic T cells is well known (47-50,64).”
In the citing paper
“Data suggest that CXCR3 is not essential for the early recruitment of CD8+ T cells into tumors (64).”
In the citing paper
“Their ligands are reported to function both as biomarkers and inducers of response to anti-PD-1 alone (64) or in combination with anti-CTLA-4 (47).”
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Citations
Cites
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A matrikine organizes the dendritic cell–T cell triads that build tertiary lymphoid structuresPreprint
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Metadata
- Authors
- Chow, M. T., Ozga, A. J., Servis, R. L., Frederick, D. T., Lo, J. A., Fisher, D. E., Freeman, G. J., Boland, G. M., & Luster, A. D.
- Affiliations
- Harvard University (US)
- Corresponding author
- Luster, Andrew D.
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2019-06
- Volume
- 50
- Issue
- 6
- Pages
- 1498-1512.e5
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC6527362
- OpenAlex
- W2945224722
- Cited by
- 716
- References
- 57
- Citations by year
- 2026: 83 · 2025: 98 · 2024: 120 · 2023: 128 · 2022: 96 · 2021: 90 · 2020: 81 · 2019: 19
- FWCI
- 30.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (AR043369)
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
- National Institutes of Health (AR043369, CA204028, AI112521, CA222871, CA163222)
- Melanoma Research Alliance
- Cancer Research Institute
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- CXCR3, CXCL9, anti-PD-1 therapy, chemokine system, CD8+ T cells, CD103+ dendritic cells, dendritic cell-T cell interaction, tumor microenvironment, melanoma, predictive biomarkers, immunotherapy resistance
- MeSH terms
- Antineoplastic Agents, Immunological, Animals, Disease Models, Animal, Humans, Lymphocyte Activation, Neoplasms, Biomarkers, T-Lymphocyte Subsets, Mice, Knockout, CD8-Positive T-Lymphocytes, Xenograft Model Antitumor Assays, Epigenesis, Genetic, Mice, Receptors, CXCR3, Immunomodulation, Molecular Targeted Therapy, Tumor Microenvironment, Programmed Cell Death 1 Receptor
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