Generation of Myeloid Cells in Cancer: The Spleen Matters

Wu, Chong; Hua, Qiaomin; Zheng, Limin

doi:10.3389/fimmu.2020.01126

Cited by 51 publications

(48 citation statements)

References 155 publications

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“…Spleen enlargement is associated with tumor-induced increase in myeloid cells [ 20 , 38 , 39 , 40 ]. Solid tumor cells crosstalk with the HSCs of the bone marrow leading to hematopoiesis and myeloid skewing of the HSCs [ 22 , 41 ].…”

Section: Resultsmentioning

confidence: 99%

Bone Marrow Homeostasis Is Impaired via JAK/STAT and Glucocorticoid Signaling in Cancer Cachexia Model

Choi

Park

et al. 2021

Cancers

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Cancer cachexia is a multifactorial systemic inflammation disease caused by complex interactions between the tumor and host tissues via soluble factors. However, whether cancer cachexia affects the bone marrow, in particular the hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs), remains unclear. Here, we investigated the bone marrow and bone in a cancer cachexia animal model generated by transplanting Lewis lung carcinoma cells. The number of bone marrow mononuclear cells (BM-MNCs) started to significantly decrease in the cancer cachectic animal model prior to the discernable loss of muscle and fat. This decrease in BM-MNCs was associated with myeloid skewing in the circulation and the expansion of hematopoietic progenitors in the bone marrow. Bone loss occurred in the cancer cachexia animal model and accompanied the decrease in the bone marrow MSCs that play important roles in both supporting HSCs and maintaining bone homeostasis. Glucocorticoid signaling mediated the decrease in bone marrow MSCs in the cancer cachectic environment. The cancer cachexia environment also skewed the differentiation of the bone marrow MSCs toward adipogenic fate via JAK/STAT as well as glucocorticoid signaling. Our results suggest that the bone loss induced in cancer cachexia is associated with the depletion and the impaired differentiation capacity of the bone marrow MSCs.

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Section: Resultsmentioning

confidence: 99%

Bone Marrow Homeostasis Is Impaired via JAK/STAT and Glucocorticoid Signaling in Cancer Cachexia Model

Choi

Park

et al. 2021

Cancers

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“…Cancer cells and tumor-associated stromal cells reprogram hematopoiesis and promote the polarization of immune cells toward suppressive phenotypes. In cancer, the spleen is a key organ of extramedullary hematopoiesis and is responsible for the production of suppressive immune cells [ 98 ]. It is well established that cancer dysregulates hematopoiesis to generate MDSCs that suppress antitumor response [ 10 , 99 ].…”

Section: The Role Of Erythroid Progenitor Cells In Cancermentioning

confidence: 99%

Tumor Immune Evasion Induced by Dysregulation of Erythroid Progenitor Cells Development

Grzywa

Justyniarska

Nowis

et al. 2021

Cancers

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Cancer cells harness normal cells to facilitate tumor growth and metastasis. Within this complex network of interactions, the establishment and maintenance of immune evasion mechanisms are crucial for cancer progression. The escape from the immune surveillance results from multiple independent mechanisms. Recent studies revealed that besides well-described myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs) or regulatory T-cells (Tregs), erythroid progenitor cells (EPCs) play an important role in the regulation of immune response and tumor progression. EPCs are immature erythroid cells that differentiate into oxygen-transporting red blood cells. They expand in the extramedullary sites, including the spleen, as well as infiltrate tumors. EPCs in cancer produce reactive oxygen species (ROS), transforming growth factor β (TGF-β), interleukin-10 (IL-10) and express programmed death-ligand 1 (PD-L1) and potently suppress T-cells. Thus, EPCs regulate antitumor, antiviral, and antimicrobial immunity, leading to immune suppression. Moreover, EPCs promote tumor growth by the secretion of growth factors, including artemin. The expansion of EPCs in cancer is an effect of the dysregulation of erythropoiesis, leading to the differentiation arrest and enrichment of early-stage EPCs. Therefore, anemia treatment, targeting ineffective erythropoiesis, and the promotion of EPC differentiation are promising strategies to reduce cancer-induced immunosuppression and the tumor-promoting effects of EPCs.

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“…Intrigued by these findings we set out to further investigate the changes in immune status in mice injected with 4T1 or 4T-Bone. Since the spleen is a major site of extramedullary hematopoiesis and was shown to be an origin of MDSCs in cancer 35 , we focused our further analyses on both BM and spleen. Interestingly, we observed significant splenomegaly in mice injected in 4T-Bone (Fig.…”

Section: Resultsmentioning

confidence: 99%

Bone metastasis is associated with acquisition of mesenchymal phenotype and immune suppression in a model of spontaneous breast cancer metastasis

Monteran

Ershaid

Sabah

et al. 2020

Sci Rep

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The most common site of breast cancer metastasis is the bone, occurring in approximately 70% of patients with advanced disease. Bone metastasis is associated with severe morbidities and high mortality. Therefore, deeper understanding of the mechanisms that enable bone-metastatic relapse are urgently needed. We report the establishment and characterization of a bone-seeking variant of breast cancer cells that spontaneously forms aggressive bone metastases following surgical resection of primary tumor. We characterized the modifications in the immune milieu during early and late stages of metastatic relapse and found that the formation of bone metastases is associated with systemic changes, as well as modifications of the bone microenvironment towards an immune suppressive milieu. Furthermore, we characterized the intrinsic changes in breast cancer cells that facilitate bone-tropism and found that they acquire mesenchymal and osteomimetic features. This model provides a clinically relevant platform to study the functional interactions between breast cancer cells and the bone microenvironment, in an effort to identify novel targets for intervention.

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Generation of Myeloid Cells in Cancer: The Spleen Matters

Cited by 51 publications

References 155 publications

Bone Marrow Homeostasis Is Impaired via JAK/STAT and Glucocorticoid Signaling in Cancer Cachexia Model

Bone Marrow Homeostasis Is Impaired via JAK/STAT and Glucocorticoid Signaling in Cancer Cachexia Model

Tumor Immune Evasion Induced by Dysregulation of Erythroid Progenitor Cells Development

Bone metastasis is associated with acquisition of mesenchymal phenotype and immune suppression in a model of spontaneous breast cancer metastasis

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