Distinct Populations of Immune-Suppressive Macrophages Differentiate from Monocytic Myeloid-Derived Suppressor Cells in Cancer

Kwak, Taekyoung; Wang, Fang; Deng, Hui; Condamine, Thomas; Kumar, Vinit; Perego, Michela; Kossenkov, Andrew V.; Montaner, Luis J.; Xu, Xiaowei; Xu, Wei; Zheng, Cathy; Schuchter, Lynn M.; Amaravadi, Ravi K.; Mitchell, Tara C.; Karakousis, Giorgos C.; Mulligan, Charles; Nam, Brian; Masters, Gregory A.; Hockstein, Neil; Bennett, Joseph; Nefedova, Yulia; Gabrilovich, Dmitry I.

doi:10.1016/j.celrep.2020.108571

Cited by 118 publications

(109 citation statements)

References 70 publications

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“…Since there were no tumors available for profiling the role of the immune compartment, we used the data from the TCGA to investigate the role of the immune cells. Consistent with the observations in 4T1/67NR mouse models, breast tumors with signatures of low CD81 + CD63 + EVs had a significantly higher frequency of M2 macrophages (known to differentiate from M-MDSCs [52]) compared with tumors with signatures of high CD81 + CD63 + EVs. By identifying and implementing signatures of CD81 + CD63 + EVs within the TCGA, we were able to circumvent the differences in the immune microenvironment in mouse tumors such as 4T1 and human breast cancers.…”

Section: Discussionsupporting

confidence: 86%

Single-Cell Cloning of Breast Cancer Cells Secreting Specific Subsets of Extracellular Vesicles

Fathi

Joseph

Adolacion

et al. 2021

Cancers

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Extracellular vesicles (EVs) mediate communication in health and disease. Conventional assays are limited in profiling EVs secreted from large populations of cells and cannot map EV secretion onto individual cells and their functional profiles. We developed a high-throughput single-cell technique that enabled the mapping of dynamics of EV secretion. By utilizing breast cancer cell lines, we established that EV secretion is heterogeneous at the single-cell level and that non-metastatic cancer cells can secrete specific subsets of EVs. Single-cell RNA sequencing confirmed that pathways related to EV secretion were enriched in the non-metastatic cells compared with metastatic cells. We established isogenic clonal cell lines from non-metastatic cells with differing propensities for CD81+CD63+EV secretion and showed for the first time that specificity in EV secretion is an inheritable property preserved during cell division. Combined in vitro and animal studies with these cell lines suggested that CD81+CD63+EV secretion can impede tumor formation. In human non-metastatic breast tumors, tumors enriched in signatures of CD81+CD63+EV have a better prognosis, higher immune cytolytic activity, and enrichment of pro-inflammatory macrophages compared with tumors with low CD81+CD63+EVs signatures. Our single-cell methodology enables the direct integration of EV secretion with multiple cellular functions and enables new insights into cell/disease biology.

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Section: Discussionsupporting

confidence: 86%

Single-Cell Cloning of Breast Cancer Cells Secreting Specific Subsets of Extracellular Vesicles

Fathi

Joseph

Adolacion

et al. 2021

Cancers

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“…Macrophages that are differentiated from M-MDSCs but not monocytes are immunosuppressive and share similar genomic profiles. Kwak et al demonstrated that the immunosuppressive activity of M-MDSC-derived macrophages is dependent on prolonged expression of S100A9 protein in these cells and involves the transcription factor C/EBPβ ( 52 ). The authors also demonstrated that S100A9 promotes M2 polarization of macrophages.…”

Section: Discussionmentioning

confidence: 99%

Bundibugyo ebolavirus Survival Is Associated with Early Activation of Adaptive Immunity and Reduced Myeloid-Derived Suppressor Cell Signaling

Woolsey

Borisevich

Agans

et al. 2021

mBio

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“…In addition to PMN-MDSCs, another subtype of MDSCs, which is morphologically similar to monocytes (monocytic MDSCs; M-MDSCs), was identified in tumor-bearing hosts. Kwak et al reported that M-MDSCs could differentiate into tumor-promoting macrophages, which are characterized by the expression of S100A9 [ 54 ].…”

Section: Cell Types Engaged In Cancer-associated Inflammationmentioning

confidence: 99%

Inflammation-Induced Tumorigenesis and Metastasis

Hibino

Kawazoe

Kasahara

et al. 2021

IJMS

123

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Inflammation, especially chronic inflammation, plays a pivotal role in tumorigenesis and metastasis through various mechanisms and is now recognized as a hallmark of cancer and an attractive therapeutic target in cancer. In this review, we discuss recent advances in molecular mechanisms of how inflammation promotes tumorigenesis and metastasis and suppresses anti-tumor immunity in various types of solid tumors, including esophageal, gastric, colorectal, liver, and pancreatic cancer as well as hematopoietic malignancies.

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Distinct Populations of Immune-Suppressive Macrophages Differentiate from Monocytic Myeloid-Derived Suppressor Cells in Cancer

Cited by 118 publications

References 70 publications

Single-Cell Cloning of Breast Cancer Cells Secreting Specific Subsets of Extracellular Vesicles

Single-Cell Cloning of Breast Cancer Cells Secreting Specific Subsets of Extracellular Vesicles

Bundibugyo ebolavirus Survival Is Associated with Early Activation of Adaptive Immunity and Reduced Myeloid-Derived Suppressor Cell Signaling

Inflammation-Induced Tumorigenesis and Metastasis

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