Myeloid Cells in Cancer Progression: Unique Subtypes and Their Roles in Tumor Growth, Vascularity, and Host Immune Suppression

Young, Pampee P.; Ardestani, Shidrokh; Li, Bin

doi:10.1007/s12307-010-0045-4

Cited by 13 publications

(8 citation statements)

References 119 publications

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“…8A ). In contrast, F4/80, a late differentiation myeloid marker [40] , was only weakly detected in these cells ( Fig. 8A ).…”

Section: Resultsmentioning

confidence: 92%

“…1A shows that resident macrophages can be split into two populations (labeled as Ctrl-P1 and Ctrl-P2) whereas after LPS-induced population can be subdivided into three subsets with distinct scatter properties (designated as LPS-P1, LPS-P2 and LPS-P3). LPS-P1 was likely comprised of mature macrophages as indicated by their large size, 92% positivity for F4/80 [40] and low expression of other markers ( Fig. 1 , Table 1 ).…”

Section: Resultsmentioning

confidence: 99%

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New Model of Macrophage Acquisition of the Lymphatic Endothelial Phenotype

Hall

Volk-Draper²,

Flister³

et al. 2012

PLoS ONE

107

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BackgroundMacrophage-derived lymphatic endothelial cell progenitors (M-LECPs) contribute to new lymphatic vessel formation, but the mechanisms regulating their differentiation, recruitment, and function are poorly understood. Detailed characterization of M-LECPs is limited by low frequency in vivo and lack of model systems allowing in-depth molecular analyses in vitro. Our goal was to establish a cell culture model to characterize inflammation-induced macrophage-to-LECP differentiation under controlled conditions.Methodology/Principal FindingsTime-course analysis of diaphragms from lipopolysaccharide (LPS)-treated mice revealed rapid mobilization of bone marrow-derived and peritoneal macrophages to the proximity of lymphatic vessels followed by widespread (∼50%) incorporation of M-LECPs into the inflamed lymphatic vasculature. A differentiation shift toward the lymphatic phenotype was found in three LPS-induced subsets of activated macrophages that were positive for VEGFR-3 and many other lymphatic-specific markers. VEGFR-3 was strongly elevated in the early stage of macrophage transition to LECPs but undetectable in M-LECPs prior to vascular integration. Similar transient pattern of VEGFR-3 expression was found in RAW264.7 macrophages activated by LPS in vitro. Activated RAW264.7 cells co-expressed VEGF-C that induced an autocrine signaling loop as indicated by VEGFR-3 phosphorylation inhibited by a soluble receptor. LPS-activated RAW264.7 macrophages also showed a 68% overlap with endogenous CD11b+/VEGFR-3+ LECPs in the expression of lymphatic-specific genes. Moreover, when injected into LPS- but not saline-treated mice, GFP-tagged RAW264.7 cells massively infiltrated the inflamed diaphragm followed by integration into 18% of lymphatic vessels.Conclusions/SignificanceWe present a new model for macrophage-LECP differentiation based on LPS activation of cultured RAW264.7 cells. This system designated here as the “RAW model” mimics fundamental features of endogenous M-LECPs. Unlike native LECPs, this model is unrestricted by cell numbers, heterogeneity of population, and ability to change genetic composition for experimental purposes. As such, this model can provide a valuable tool for understanding the LECP and lymphatic biology.

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“…8A ). In contrast, F4/80, a late differentiation myeloid marker [40] , was only weakly detected in these cells ( Fig. 8A ).…”

Section: Resultsmentioning

confidence: 92%

Section: Resultsmentioning

confidence: 99%

New Model of Macrophage Acquisition of the Lymphatic Endothelial Phenotype

Hall

Volk-Draper²,

Flister³

et al. 2012

PLoS ONE

107

View full text Add to dashboard Cite

show abstract

“…Myeloid cells play a central role in immune responses and are the most predominant immune cells associated with lung and other solid tumors (40), with infiltrations of myeloid cells associated with tumor metastasis and poor patient survival (41). In agreement with those previous findings, myeloid cells were readily detected surrounding endogenously arising mouse lung tumors induced by the tobacco carcinogen urethane, whereas very few myeloid cells were found in the normal lung tissues (Fig.…”

Section: Resultsmentioning

confidence: 99%

Myeloid STAT3 Promotes Lung Tumorigenesis by Transforming Tumor Immunosurveillance into Tumor-Promoting Inflammation

Zhou

Sun

et al. 2017

Cancer Immunology Research

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One of the most fundamental and challenging questions in the cancer field is how immunity in cancer patients is transformed from tumor immunosurveillance to tumor-promoting inflammation. Here, we identify the transcription factor STAT3 as the culprit responsible for this pathogenic event in lung cancer development. We found that antitumor type 1 CD4+ T helper (Th1) cells and CD8+ T cells were directly counter-balanced in lung cancer development with tumor-promoting myeloid-derived suppressor cells (MDSCs) and suppressive macrophages, and that activation of STAT3 in MDSCs and macrophages promoted tumorigenesis through pulmonary recruitment and increased resistance of suppressive cells to CD8+ T cells, enhancement of cytotoxicity towards CD4+ and CD8+ T cells, induction of regulatory T cell (Treg), inhibition of dendritic cells (DCs), and polarization of macrophages toward the M2 phenotype. The deletion of myeloid STAT3 boosted antitumor immunity and suppressed lung tumorigenesis. These findings increase our understanding of immune programming in lung tumorigenesis and provide a mechanistic basis for developing STAT3-based immunotherapy against this and other solid tumors.

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“…This is an important limitation of our study, as it prevented us from drawing any conclusion on the prognostic potential of the regulatory population of FoxP3-expressing lymphocytes. However, we suggest that the immunosuppressive capacity of the regulatory population of FoxP3-expressing lymphocytes may be important in CRC to control continuous and aggressive inflammatory responses that may favor tumor proliferation [ 52 , 53 ]. Our data are in accordance with previous data showing that high frequencies of FoxP3 + T lymphocytes are associated with early T stages and absence of lymph node involvement [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Increased CD3+, CD8+, or FoxP3+ T Lymphocyte Infiltrations Are Associated with the Pathogenesis of Colorectal Cancer but Not with the Overall Survival of Patients

Barbosa

Martinho

Nogueira

et al. 2021

Biology

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Tumor-infiltrating lymphocytes include heterogeneous populations of T lymphocytes that play crucial roles in the tumor immune response; importantly, their presence in the tumor tissue may predict clinical outcomes. Therefore, we herein studied the prognostic significance of the presence and location of CD3+, CD8+, and FoxP3+ T lymphocytes in colorectal cancer samples. In the intratumor analysis, our data did not reveal any association between lymphocyte infiltrations with clinical or pathological data. However, in the tumor margins, we found that the presence of high infiltrations of CD3+, CD8+, or FoxP3+ T lymphocytes were associated with TNM stages I-II (p = 0.021, p = 0.022, and p = 0.012, respectively) and absence of lymph node metastases (p = 0.010, p = 0.003, and p = 0.004, respectively). Despite these associations with good prognostic indicators, we were not able to find any statistically significant alterations in the overall survival of the patients, even though high infiltrations of FoxP3+ T lymphocytes in the tumor margins resulted in an increased overall survival of 14 months. Taken together, these data show that the presence of CD3+, CD8+, or FoxP3+T lymphocyte infiltrates in the tumor margins are associated with the pathogenesis of CRC, but only high Foxp3+ T lymphocyte infiltrations in the tumor invasive margins are inclined to indicate favorable prognosis.

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Myeloid Cells in Cancer Progression: Unique Subtypes and Their Roles in Tumor Growth, Vascularity, and Host Immune Suppression

Cited by 13 publications

References 119 publications

New Model of Macrophage Acquisition of the Lymphatic Endothelial Phenotype

New Model of Macrophage Acquisition of the Lymphatic Endothelial Phenotype

Myeloid STAT3 Promotes Lung Tumorigenesis by Transforming Tumor Immunosurveillance into Tumor-Promoting Inflammation

Increased CD3+, CD8+, or FoxP3+ T Lymphocyte Infiltrations Are Associated with the Pathogenesis of Colorectal Cancer but Not with the Overall Survival of Patients

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