In Vivo Labeling Resolves Distinct Temporal, Spatial, and Functional Properties of Tumor Macrophages and Identifies Subset-Specific Effects of PD-L1 Blockade Article Swipe
Colin Y.C. Lee
,
Isaac Dean
,
Nathan Richoz
,
Zhi Li
,
Bethany C. Kennedy
,
Lisa A. Vettore
,
Youhani Samarakoon
,
Kathryn Gilroy
,
Tetsuo Hasegawa
,
Gianluca Carlesso
,
Scott A. Hammond
,
Simon J. Dovedi
,
Owen J. Sansom
,
Zewen Kelvin Tuong
,
Timotheus Y.F. Halim
,
David R. Withers
,
Menna R. Clatworthy
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1158/2326-6066.cir-24-1233
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1158/2326-6066.cir-24-1233
Tumor-associated macrophages (TAM) are a universal feature of cancers but variably influence outcomes and treatment responses. In this study, we used a photoconvertible mouse to distinguish newly entering, monocyte-derived TAMs (mdTAM) that were enriched at the tumor core from resident-like TAMs that localized with fibroblasts at the tumor–normal interface. The mdTAM pool was highly dynamic and continually replenished by circulating monocytes. Upon tumor entry, these monocytes differentiated down two divergent fate trajectories distinguished by the expression of MHC class II. MHC-II+ mdTAMs were functionally distinct from MHC-II− mdTAMs, demonstrating increased capacity for endocytosis and Fc-gamma receptor–mediated phagocytosis, as well as proinflammatory cytokine production. Both mdTAM subsets showed reduced expression of inflammatory transcripts and increased expression of PD-L1 with increasing tumor dwell time. Treatment with anti–PD-L1 skewed mdTAM differentiation toward the MHC-II+ fate and attenuated the anti-inflammatory effects of the tumor environment. Anti–PD-L1 enhanced mdTAM–CD4+ T cell interactions, establishing an IFNγ-CXCL9/10–dependent positive feedback loop. Altogether, these data resolve distinct temporal, spatial, and functional properties of TAMs and provide evidence of subset-specific effects of PD-L1 blockade.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1158/2326-6066.cir-24-1233
- https://aacrjournals.org/cancerimmunolres/article-pdf/doi/10.1158/2326-6066.CIR-24-1233/3621788/cir-24-1233.pdf
- OA Status
- hybrid
- Cited By
- 2
- References
- 2
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4411330342
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4411330342Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1158/2326-6066.cir-24-1233Digital Object Identifier
- Title
-
In Vivo Labeling Resolves Distinct Temporal, Spatial, and Functional Properties of Tumor Macrophages and Identifies Subset-Specific Effects of PD-L1 BlockadeWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-06-16Full publication date if available
- Authors
-
Colin Y.C. Lee, Isaac Dean, Nathan Richoz, Zhi Li, Bethany C. Kennedy, Lisa A. Vettore, Youhani Samarakoon, Kathryn Gilroy, Tetsuo Hasegawa, Gianluca Carlesso, Scott A. Hammond, Simon J. Dovedi, Owen J. Sansom, Zewen Kelvin Tuong, Timotheus Y.F. Halim, David R. Withers, Menna R. ClatworthyList of authors in order
- Landing page
-
https://doi.org/10.1158/2326-6066.cir-24-1233Publisher landing page
- PDF URL
-
https://aacrjournals.org/cancerimmunolres/article-pdf/doi/10.1158/2326-6066.CIR-24-1233/3621788/cir-24-1233.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
hybridOpen access status per OpenAlex
- OA URL
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https://aacrjournals.org/cancerimmunolres/article-pdf/doi/10.1158/2326-6066.CIR-24-1233/3621788/cir-24-1233.pdfDirect OA link when available
- Concepts
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Biology, MHC class I, In vivo, Immunology, Cancer research, Major histocompatibility complex, Immunotherapy, MHC class II, Cell biology, Blockade, Cytokine, Monocyte, Immune system, Receptor, GeneticsTop concepts (fields/topics) attached by OpenAlex
- Cited by
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2Total citation count in OpenAlex
- Citations by year (recent)
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2025: 2Per-year citation counts (last 5 years)
- References (count)
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2Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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