Measuring Suppressive Activity and Autophagy in Myeloid-Derived Suppressor Cells

Papaioannou, Antonis Stylianos; Boumpas, Athina; Papadopoulou, Miranta; Hatzioannou, Aikaterini; Alissafi, Themis; Verginis, Panayotis

doi:10.1007/978-1-0716-1060-2_9

Cited by 4 publications

(1 citation statement)

References 17 publications

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“…For the suppression assay of MDSC subsets, CD4 + Foxp3 - effector T cells (Teff) were sorted from the LNs of naïve Foxp3 EGFP .KI mice, as described previously (60, 61), and stained with the division-tracking dye CellTrace CFSE (Invitrogen, #C34554) according to the manufacturer’s protocol. In summary, a total of 75 × 10 3 labeled Teff cells were seeded in 96-well round-bottom plate in each well supplemented with Dynabeads™ Mouse T-Activator CD3/CD28 (Gibco, #11456D) at ration 1:1 beads to Teff cells.…”

Section: Methodsmentioning

confidence: 99%

PD-L1 blockade immunotherapy rewires cancer emergency myelopoiesis

Boumpas,

Papaioannou,

Bousounis

et al. 2023

Preprint

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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. Herein, we reveal that immunotherapy with PD-L1 blockage antibody (αPDL1) in tumour-bearing mice targets the hematopoietic stem and progenitor cells (HSPCs) in the bone marrow (ΒΜ), mediating their exit from quiescence and promoting their proliferation. Notably, disruption of the PDL1/PD1 axis induces transcriptomic reprogramming in HSPCs, from both individuals with Hodgkin lymphoma (HL) and tumour-bearing mice shifting towards an inflammatory state. Functionally, transplantation of HSPCs isolated from αPDL1-treated tumor-bearing mice exhibited resistance to cancer-associated myelopoiesis as evident by the generation of reduced frequencies of myeloid-derived suppressor cells (MDSCs) compared to cells from control-treated mice. Our findings shed light on unrecognized mechanisms of action of ICB immunotherapy in cancer, which involves targeting of BM-driven HSPCs and reprogramming of emergency myelopoiesis.

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Section: Methodsmentioning

confidence: 99%

PD-L1 blockade immunotherapy rewires cancer emergency myelopoiesis

Boumpas,

Papaioannou,

Bousounis

et al. 2023

Preprint

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Blocking Dectin-1 prevents colorectal tumorigenesis by suppressing prostaglandin E2 production in myeloid-derived suppressor cells and enhancing IL-22 binding protein expression

et al. 2023

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Dectin-1 (gene Clec7a), a receptor for β-glucans, plays important roles in the host defense against fungi and immune homeostasis of the intestine. Although this molecule is also suggested to be involved in the regulation of tumorigenesis, the role in intestinal tumor development remains to be elucidated. In this study, we find that azoxymethane-dextran-sodium-sulfate-induced and ApcMin-induced intestinal tumorigenesis are suppressed in Clec7a−/− mice independently from commensal microbiota. Dectin-1 is preferentially expressed on myeloid-derived suppressor cells (MDSCs). In the Clec7a−/− mouse colon, the proportion of MDSCs and MDSC-derived prostaglandin E2 (PGE2) levels are reduced, while the expression of IL-22 binding protein (IL-22BP; gene Il22ra2) is upregulated. Dectin-1 signaling induces PGE2-synthesizing enzymes and PGE2 suppresses Il22ra2 expression in vitro and in vivo. Administration of short chain β-glucan laminarin, an antagonist of Dectin-1, suppresses the development of mouse colorectal tumors. Furthermore, in patients with colorectal cancer (CRC), the expression of CLEC7A is also observed in MDSCs and correlated with the death rate and tumor severity. Dectin-1 signaling upregulates PGE2-synthesizing enzyme expression and PGE2 suppresses IL22RA2 expression in human CRC-infiltrating cells. These observations indicate a role of the Dectin-1-PGE2-IL-22BP axis in regulating intestinal tumorigenesis, suggesting Dectin-1 as a potential target for CRC therapy.

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PD-L1 blockade immunotherapy rewires cancer-induced emergency myelopoiesis

Boumpas,

Papaioannou,

Bousounis

et al. 2024

Front. Immunol.

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IntroductionImmune 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.MethodsIn 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.ResultsHerein, 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.DiscussionOur 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.

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Measuring Suppressive Activity and Autophagy in Myeloid-Derived Suppressor Cells

Cited by 4 publications

References 17 publications

PD-L1 blockade immunotherapy rewires cancer emergency myelopoiesis

PD-L1 blockade immunotherapy rewires cancer emergency myelopoiesis

Blocking Dectin-1 prevents colorectal tumorigenesis by suppressing prostaglandin E2 production in myeloid-derived suppressor cells and enhancing IL-22 binding protein expression

PD-L1 blockade immunotherapy rewires cancer-induced emergency myelopoiesis

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