Osteoprogenitor-GMP crosstalk underpins solid tumor-induced systemic immunosuppression and persists after tumor removal
Copyright © 2023 Elsevier Inc. All rights reserved..
Remote tumors disrupt the bone marrow (BM) ecosystem (BME), eliciting the overproduction of BM-derived immunosuppressive cells. However, the underlying mechanisms remain poorly understood. Herein, we characterized breast and lung cancer-induced BME shifts pre- and post-tumor removal. Remote tumors progressively lead to osteoprogenitor (OP) expansion, hematopoietic stem cell dislocation, and CD41- granulocyte-monocyte progenitor (GMP) aggregation. The tumor-entrained BME is characterized by co-localization between CD41- GMPs and OPs. OP ablation abolishes this effect and diminishes abnormal myeloid overproduction. Mechanistically, HTRA1 carried by tumor-derived small extracellular vesicles upregulates MMP-13 in OPs, which in turn induces the alterations in the hematopoietic program. Importantly, these effects persist post-surgery and continue to impair anti-tumor immunity. Conditional knockout or inhibition of MMP-13 accelerates immune reinstatement and restores the efficacies of immunotherapies. Therefore, tumor-induced systemic effects are initiated by OP-GMP crosstalk that outlasts tumor burden, and additional treatment is required to reverse these effects for optimal therapeutic efficacy.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:30 |
|---|---|
| Enthalten in: |
Cell stem cell - 30(2023), 5 vom: 04. Mai, Seite 648-664.e8 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Hao, Xiaoxin [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 08.05.2023 Date Revised 13.12.2023 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.stem.2023.04.005 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM356497623 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM356497623 | ||
| 003 | DE-627 | ||
| 005 | 20231227131237.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.stem.2023.04.005 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1225.xml |
| 035 | |a (DE-627)NLM356497623 | ||
| 035 | |a (NLM)37146584 | ||
| 035 | |a (PII)S1934-5909(23)00123-6 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Hao, Xiaoxin |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Osteoprogenitor-GMP crosstalk underpins solid tumor-induced systemic immunosuppression and persists after tumor removal |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 08.05.2023 | ||
| 500 | |a Date Revised 13.12.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 Elsevier Inc. All rights reserved. | ||
| 520 | |a Remote tumors disrupt the bone marrow (BM) ecosystem (BME), eliciting the overproduction of BM-derived immunosuppressive cells. However, the underlying mechanisms remain poorly understood. Herein, we characterized breast and lung cancer-induced BME shifts pre- and post-tumor removal. Remote tumors progressively lead to osteoprogenitor (OP) expansion, hematopoietic stem cell dislocation, and CD41- granulocyte-monocyte progenitor (GMP) aggregation. The tumor-entrained BME is characterized by co-localization between CD41- GMPs and OPs. OP ablation abolishes this effect and diminishes abnormal myeloid overproduction. Mechanistically, HTRA1 carried by tumor-derived small extracellular vesicles upregulates MMP-13 in OPs, which in turn induces the alterations in the hematopoietic program. Importantly, these effects persist post-surgery and continue to impair anti-tumor immunity. Conditional knockout or inhibition of MMP-13 accelerates immune reinstatement and restores the efficacies of immunotherapies. Therefore, tumor-induced systemic effects are initiated by OP-GMP crosstalk that outlasts tumor burden, and additional treatment is required to reverse these effects for optimal therapeutic efficacy | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 4 | |a MDSCs | |
| 650 | 4 | |a bone marrow niches | |
| 650 | 4 | |a cancer | |
| 650 | 4 | |a hematopoiesis | |
| 650 | 4 | |a hematopoietic stem/progenitor cells | |
| 650 | 4 | |a immunotherapies | |
| 650 | 4 | |a myelopoiesis | |
| 650 | 4 | |a osteoprogenitor | |
| 650 | 4 | |a scRNA-seq | |
| 650 | 4 | |a systemic immunosuppression | |
| 650 | 7 | |a Matrix Metalloproteinase 13 |2 NLM | |
| 650 | 7 | |a EC 3.4.24.- |2 NLM | |
| 650 | 7 | |a HTRA1 protein, human |2 NLM | |
| 650 | 7 | |a EC 3.4.21.- |2 NLM | |
| 650 | 7 | |a High-Temperature Requirement A Serine Peptidase 1 |2 NLM | |
| 650 | 7 | |a EC 3.4.21.- |2 NLM | |
| 700 | 1 | |a Shen, Yichao |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Nan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Weijie |e verfasserin |4 aut | |
| 700 | 1 | |a Valverde, Elizabeth |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Ling |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Hilda L |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Zhan |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Liqun |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Bado, Igor |e verfasserin |4 aut | |
| 700 | 1 | |a Michie, Laura Natalee |e verfasserin |4 aut | |
| 700 | 1 | |a Rivas, Charlotte Helena |e verfasserin |4 aut | |
| 700 | 1 | |a Dominguez, Luis Becerra |e verfasserin |4 aut | |
| 700 | 1 | |a Aguirre, Sergio |e verfasserin |4 aut | |
| 700 | 1 | |a Pingel, Bradley C |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Yi-Hsuan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Fengshuo |e verfasserin |4 aut | |
| 700 | 1 | |a Ding, Yunfeng |e verfasserin |4 aut | |
| 700 | 1 | |a Edwards, David G |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Alexander, Angela |e verfasserin |4 aut | |
| 700 | 1 | |a Ueno, Naoto T |e verfasserin |4 aut | |
| 700 | 1 | |a Hsueh, Po-Ren |e verfasserin |4 aut | |
| 700 | 1 | |a Tu, Chih-Yen |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Liang-Chih |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Shu-Hsia |e verfasserin |4 aut | |
| 700 | 1 | |a Hung, Mien-Chie |e verfasserin |4 aut | |
| 700 | 1 | |a Lim, Bora |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xiang H-F |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cell stem cell |d 2007 |g 30(2023), 5 vom: 04. Mai, Seite 648-664.e8 |w (DE-627)NLM176526269 |x 1875-9777 |7 nnns |
| 773 | 1 | 8 | |g volume:30 |g year:2023 |g number:5 |g day:04 |g month:05 |g pages:648-664.e8 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.stem.2023.04.005 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 30 |j 2023 |e 5 |b 04 |c 05 |h 648-664.e8 | ||