PD-L1 blockade immunotherapy rewires cancer-induced emergency myelopoiesis
Abstract: Introduction: Immune checkpoint blockade (ICB) immunotherapy has revolutionized cancer treatment, demonstrating exceptional clinical responses in a wide range of cancers. Despite the success, a significant proportion of patients still fail to respond, highlighting the existence of unappreciated mechanisms of immunotherapy resistance. Delineating such mechanisms is paramount to minimize immunotherapy failures and optimize the clinical benefit.
Methods: In this study, we treated tumour-bearing mice with PD-L1 blockage antibody (aPD-L1) immunotherapy, to investigate its effects on cancer-induced emergency myelopoiesis, focusing on bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs). We examined the impact of aPD-L1 treatment on HSPC quiescence, proliferation, transcriptomic profile, and functionality.
Results: Herein, we reveal that aPD-L1 in tumour-bearing mice targets the HSPCs in the BM, mediating their exit from quiescence and promoting their proliferation. Notably, disruption of the PDL1/PD1 axis induces transcriptomic reprogramming in HSPCs, observed in both individuals with Hodgkin lymphoma (HL) and tumour-bearing mice, shifting towards an inflammatory state. Furthermore, HSPCs from aPDL1-treated mice demonstrated resistance to cancer-induced emergency myelopoiesis, evidenced by a lower generation of MDSCs compared to control-treated mice.
Discussion: Our findings shed light on unrecognized mechanisms of action of ICB immunotherapy in cancer, which involves targeting of BM-driven HSPCs and reprogramming of cancer-induced emergency myelopoiesis
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Notes
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Frontiers in immunology. - 15 (2024) , 1386838, ISSN: 1664-3224
- Event
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Veröffentlichung
- (where)
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Freiburg
- (who)
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Universität
- (when)
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2024
- Creator
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Boumpas, Athina
Papaioannou, Antonis S.
Bousounis, Pavlos
Grigoriou, Maria
Bergo, Veronica
Papafragkos, Iosif
Tasis, Athanasios
Iskas, Michael
Boon, Louis
Makridakis, Manousos
Vlachou, Antonia
Gavriilaki, Eleni
Hatzioannou, Aikaterini
Mitroulis, Ioannis
Trompouki, Eirini
Verginis, Panayotis
- DOI
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10.3389/fimmu.2024.1386838
- URN
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urn:nbn:de:bsz:25-freidok-2609078
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:36 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Boumpas, Athina
- Papaioannou, Antonis S.
- Bousounis, Pavlos
- Grigoriou, Maria
- Bergo, Veronica
- Papafragkos, Iosif
- Tasis, Athanasios
- Iskas, Michael
- Boon, Louis
- Makridakis, Manousos
- Vlachou, Antonia
- Gavriilaki, Eleni
- Hatzioannou, Aikaterini
- Mitroulis, Ioannis
- Trompouki, Eirini
- Verginis, Panayotis
- Universität
Time of origin
- 2024
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