TNF-α-Secreting Lung Tumor-Infiltrated Monocytes Play a Pivotal Role During Anti-PD-L1 Immunotherapy Article Swipe
Kirsten De Ridder
,
Hanne Locy
,
Elisa Piccioni
,
Miren Zuazo
,
Robin Maximilian Awad
,
Stefaan Verhulst
,
Mathias Van Bulck
,
Yannick De Vlaeminck
,
Quentin Lecocq
,
Eva Reijmen
,
Wout de Mey
,
Lien De Beck
,
Thomas Ertveldt
,
Isabel Pintelon
,
Jean‐Pierre Timmermans
,
David Escors
,
Marleen Keyaerts
,
Karine Breckpot
,
Cleo Goyvaerts
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.3389/fimmu.2022.811867
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.3389/fimmu.2022.811867
Immune checkpoint blockade (ICB) of the PD-1 pathway revolutionized the survival forecast for advanced non-small cell lung cancer (NSCLC). Yet, the majority of PD-L1 + NSCLC patients are refractory to anti-PD-L1 therapy. Recent observations indicate a pivotal role for the PD-L1 + tumor-infiltrating myeloid cells in therapy failure. As the latter comprise a heterogenous population in the lung tumor microenvironment, we applied an orthotopic Lewis Lung Carcinoma (LLC) model to evaluate 11 different tumor-residing myeloid subsets in response to anti-PD-L1 therapy. While we observed significantly reduced fractions of tumor-infiltrating MHC-II low macrophages and monocytes, serological levels of TNF-α restored in lung tumor-bearing mice. Notably, we demonstrated in vivo and in vitro that anti-PD-L1 therapy mediated a monocyte-specific production of, and response to TNF-α, further accompanied by their significant upregulation of CD80, VISTA, LAG-3, SIRP-α and TIM-3. Nevertheless, co-blockade of PD-L1 and TNF-α did not reduce LLC tumor growth. A phenomenon that was partly explained by the observation that monocytes and TNF-α play a Janus-faced role in anti-PD-L1 therapy-mediated CTL stimulation. This was endorsed by the observation that monocytes appeared crucial to effectively boost T cell-mediated LLC killing in vitro upon combined PD-L1 with LAG-3 or SIRP-α blockade. Hence, this study enlightens the biomarker potential of lung tumor-infiltrated monocytes to define more effective ICB combination strategies.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3389/fimmu.2022.811867
- https://www.frontiersin.org/articles/10.3389/fimmu.2022.811867/pdf
- OA Status
- gold
- Cited By
- 18
- References
- 56
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4224081925
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4224081925Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3389/fimmu.2022.811867Digital Object Identifier
- Title
-
TNF-α-Secreting Lung Tumor-Infiltrated Monocytes Play a Pivotal Role During Anti-PD-L1 ImmunotherapyWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2022Year of publication
- Publication date
-
2022-04-14Full publication date if available
- Authors
-
Kirsten De Ridder, Hanne Locy, Elisa Piccioni, Miren Zuazo, Robin Maximilian Awad, Stefaan Verhulst, Mathias Van Bulck, Yannick De Vlaeminck, Quentin Lecocq, Eva Reijmen, Wout de Mey, Lien De Beck, Thomas Ertveldt, Isabel Pintelon, Jean‐Pierre Timmermans, David Escors, Marleen Keyaerts, Karine Breckpot, Cleo GoyvaertsList of authors in order
- Landing page
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https://doi.org/10.3389/fimmu.2022.811867Publisher landing page
- PDF URL
-
https://www.frontiersin.org/articles/10.3389/fimmu.2022.811867/pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
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https://www.frontiersin.org/articles/10.3389/fimmu.2022.811867/pdfDirect OA link when available
- Concepts
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Immunotherapy, Tumor necrosis factor alpha, Medicine, Immunology, PD-L1, Lung, Monocyte, Cancer research, Immune system, Internal medicineTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
18Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 2, 2024: 5, 2023: 8, 2022: 3Per-year citation counts (last 5 years)
- References (count)
-
56Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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