Human <i>KIT</i>+ myeloid cells facilitate visceral metastasis by melanoma

Yu, Chun I.; Martínek, Jan; Wu, Te-Chia; Kim, Kyung In; George, Joshy; Ahmadzadeh, Elaheh; Maser, Richard S.; Marches, Florentina; Metang, Patrick; Authié, Pierre; Oliveira, Vanessa K.P.; Wang, Victor G.; Chuang, Jeffrey H.; Robson, Paul; Banchereau, Jacques; Palucka, Karolina

doi:10.1084/jem.20182163

Cited by 7 publications

(6 citation statements)

References 44 publications

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“…However, the development of functional human macrophages in HSPC-engrafted MISTRG mice also caused anemia and loss of reconstitution over time, which limits the time available to perform experiments and evaluate the efficacy of therapies [18]. Human KIT + myeloid cells were shown to facilitate metastasis in melanoma CDX NSG-SGM3 but not NSG humanized mice, which lack human factors that promote efficient human myeloid cell development [92,198]. In both, MISTRG and NSG-SGM3 humanized mouse models, the melanoma-infiltrating myeloid cells were transcriptionally similar to myeloid cells found in melanoma patients [19,198].…”

Section: Humanized Pdx Mouse Models For Preclinical Testing Of Cancer...mentioning

confidence: 99%

“…Human KIT + myeloid cells were shown to facilitate metastasis in melanoma CDX NSG-SGM3 but not NSG humanized mice, which lack human factors that promote efficient human myeloid cell development [92,198]. In both, MISTRG and NSG-SGM3 humanized mouse models, the melanoma-infiltrating myeloid cells were transcriptionally similar to myeloid cells found in melanoma patients [19,198]. Using a NOD/SCID humanized mouse model, Su et al demonstrated that CCL18 usually produced by TAMs contributes to epithelial-mesenchymal transition (EMT) and metastasis in a breast cancer CDX model [199].…”

Section: Humanized Pdx Mouse Models For Preclinical Testing Of Cancer...mentioning

confidence: 99%

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Modeling the Tumor Microenvironment and Cancer Immunotherapy in Next-Generation Humanized Mice

Chen,

Neuwirth,

Herndler-Brandstetter

2023

Cancers

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Cancer immunotherapy has brought significant clinical benefits to numerous patients with malignant disease. However, only a fraction of patients experiences complete and durable responses to currently available immunotherapies. This highlights the need for more effective immunotherapies, combination treatments and predictive biomarkers. The molecular properties of a tumor, intratumor heterogeneity and the tumor immune microenvironment decisively shape tumor evolution, metastasis and therapy resistance and are therefore key targets for precision cancer medicine. Humanized mice that support the engraftment of patient-derived tumors and recapitulate the human tumor immune microenvironment of patients represent a promising preclinical model to address fundamental questions in precision immuno-oncology and cancer immunotherapy. In this review, we provide an overview of next-generation humanized mouse models suitable for the establishment and study of patient-derived tumors. Furthermore, we discuss the opportunities and challenges of modeling the tumor immune microenvironment and testing a variety of immunotherapeutic approaches using human immune system mouse models.

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Section: Humanized Pdx Mouse Models For Preclinical Testing Of Cancer...mentioning

confidence: 99%

Section: Humanized Pdx Mouse Models For Preclinical Testing Of Cancer...mentioning

confidence: 99%

Modeling the Tumor Microenvironment and Cancer Immunotherapy in Next-Generation Humanized Mice

Chen,

Neuwirth,

Herndler-Brandstetter

2023

Cancers

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“…In addition, our group has identified a consistent, but yet not fully characterized, Mϕ subpopulation that is enriched in metastatic melanomas with poor prognosis and immunosuppressed tumor microenvironment [147]. Moreover, scRNA-Seq analysis identified a gene signature of myeloid cells that facilitate metastasis in melanoma [148]. Nevertheless, due to their inflammatory activity, activated Mϕ have been used in vitro and in vivo to help target melanoma cells.…”

Section: Melanomamentioning

confidence: 99%

Hallmarks of Aging in Macrophages: Consequences to Skin Inflammaging

Guimarães

Almeida

Santos

et al. 2021

Cells

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The skin is our largest organ and the outermost protective barrier. Its aging reflects both intrinsic and extrinsic processes resulting from the constant insults it is exposed to. Aging in the skin is accompanied by specific epigenetic modifications, accumulation of senescent cells, reduced cellular proliferation/tissue renewal, altered extracellular matrix, and a proinflammatory environment favoring undesirable conditions, including disease onset. Macrophages (Mφ) are the most abundant immune cell type in the skin and comprise a group of heterogeneous and plastic cells that are key for skin homeostasis and host defense. However, they have also been implicated in orchestrating chronic inflammation during aging. Since Mφ are related to innate and adaptive immunity, it is possible that age-modified skin Mφ promote adaptive immunity exacerbation and exhaustion, favoring the emergence of proinflammatory pathologies, such as skin cancer. In this review, we will highlight recent findings pertaining to the effects of aging hallmarks over Mφ, supporting the recognition of such cell types as a driving force in skin inflammaging and age-related diseases. We will also present recent research targeting Mφ as potential therapeutic interventions in inflammatory skin disorders and cancer.

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“…We demonstrate here that these deficiencies can be ameliorated in the newly developed NSG-SGM3 mice, which transgenically express three human cytokine/chemokine genes IL-3, GM-CSF, and KITLG. The expression of these genes improves the differentiation and maturation of the myeloid cells [25][26][27][28][29] . The present study is aimed at establishing a reliable new-generation, humanized mouse model for the HIV/Mtb co-infection research.…”

Section: Introductionmentioning

confidence: 99%

A Novel Humanized Mouse Model for HIV and Tuberculosis Co-infection Studies

Bohórquez,

Adduri,

Ansari

et al. 2024

Preprint

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Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), continues to be a major public health problem worldwide. The human immunodeficiency virus (HIV) is another equally important life-threatening pathogen. Further, co-infections with HIV and Mtb have severe effects in the host, with people infected with HIV being fifteen to twenty-one times more likely to develop active TB. The use of an appropriate animal model for HIV/Mtb co-infection that can recapitulate the diversity of the immune response in humans would be a useful tool for conducting basic and translational research in HIV/Mtb infections. The present study was focused on developing a humanized mouse model for investigations on HIV-Mtb co-infection. Using NSG-SGM3 mice that can engraft human stem cells, our studies showed that they were able to engraft human CD34+ stem cells which then differentiate into a full-lineage of human immune cell subsets. After co-infection with HIV and Mtb, these mice showed decrease in CD4+ T cell counts overtime and elevated HIV load in the sera, similar to the infection pattern of humans. Additionally, Mtb caused infections in both lungs and spleen, and induced the development of granulomatous lesions in the lungs, detected by CT scan and histopathology. Distinct metabolomic profiles were also observed in the tissues from different mouse groups after co-infections. Our results suggest that the humanized NSG-SGM3 mice are able to recapitulate the effects of HIV and Mtb infections and co-infection in the human host at pathological, immunological and metabolism levels, providing a dependable small animal model for studying HIV/Mtb co-infection.

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Human KIT+ myeloid cells facilitate visceral metastasis by melanoma

Cited by 7 publications

References 44 publications

Modeling the Tumor Microenvironment and Cancer Immunotherapy in Next-Generation Humanized Mice

Modeling the Tumor Microenvironment and Cancer Immunotherapy in Next-Generation Humanized Mice

Hallmarks of Aging in Macrophages: Consequences to Skin Inflammaging

A Novel Humanized Mouse Model for HIV and Tuberculosis Co-infection Studies

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