The Multifaceted Role of Perivascular Macrophages in Tumors

Lewis, Claire E.; Harney, Allison S.; Pollard, Jeffrey W.

doi:10.1016/j.ccell.2016.05.017

Cited by 216 publications

(215 citation statements)

References 85 publications

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“…7 , 12 Immune cells, which often infiltrate tumors and preneoplastic lesions, also produce a variety of cytokines and chemokines that propagate a localized inflammatory response and enhance premalignant cell growth and survival by activating signaling pathways such as nuclear factor (NF)-κB or mitogen-activated protein kinases (MAPKs). 7 , 13-16 However, the underlying mechanisms that link these chronic inflammatory states to colorectal cancer development need to be further explored.…”

Section: Introductionmentioning

confidence: 99%

S100A4 promotes colon inflammation and colitis-associated colon tumorigenesis

Zhang

Hou

et al. 2018

OncoImmunology

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S100A4 plays important roles in tumor development and metastasis, but its role in regulating inflammation and colitis-associated tumorigenesis has not been well characterized. Here, we report that S100A4 expression was increased in azoxymethane (AOM) and dextran sulfate sodium (DSS) induced colorectal cancer (CRC) in mice. After AOM/DSS treatment, both S100A4-TK mice with the selective depletion of S100A4-expressing cells and S100A4-deficient (S100A4−/−) mice developed fewer and smaller tumors than wild-type (WT) control littermates. Furthermore, S100A4−/− mice were resistant to DSS-induced colitis, reduced infiltration of macrophages, and the diminished production of proinflammatory cytokines. Further studies revealed that reduced colon inflammation and colorectal tumor development in S100A4−/− mice were partly due to the dampening of nuclear factor (NF)-κB activation in macrophages. Furthermore, the administration of a neutralizing S100A4 antibody to WT mice significantly decreased AOM/DSS-induced colon inflammation and tumorigenesis. These results indicate that S100A4 amplifies an inflammatory microenvironment that promotes colon tumorigenesis and provides a promising therapeutic strategy for treatment of inflammatory bowel disease and prevention of colitis-associated colorectal carcinogenesis.

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Section: Introductionmentioning

confidence: 99%

S100A4 promotes colon inflammation and colitis-associated colon tumorigenesis

Zhang

Hou

et al. 2018

OncoImmunology

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“…Free radicals damage the DNA of normal cells, and the genome loses stability and results in a transformation into cancer cells (15). Other notable stages in cancer progression include cancer cell invasion, angiogenesis, metastasis and suppression of adaptive anti-tumor immunity (7,9,16). Tumor-associated macrophages (TAMs) are involved in these stages.…”

Section: Macrophages-general Function In Carcinogenesismentioning

confidence: 99%

“…Tumor-associated macrophages (TAMs) are involved in these stages. TAMs are formed from monocytes circulating in the blood (16). With the help of multiple different cytokines including CSF-1, C-C motif chemokine ligand 2 (CCL-2), IL-34, vascular endothelial growth factor A (VEGFA) or C-X-C motif chemokine ligand 12 (CXCL12) produced by cancer cells as they infiltrate the tumor through the vessels (16).…”

Section: Macrophages-general Function In Carcinogenesismentioning

confidence: 99%

“…TAMs are formed from monocytes circulating in the blood (16). With the help of multiple different cytokines including CSF-1, C-C motif chemokine ligand 2 (CCL-2), IL-34, vascular endothelial growth factor A (VEGFA) or C-X-C motif chemokine ligand 12 (CXCL12) produced by cancer cells as they infiltrate the tumor through the vessels (16). They accumulate in the invasive tumor edge, cancer cell/stromal border, central tumor mass, hypoxic/necrotic regions and perivascular areas (16).…”

Section: Macrophages-general Function In Carcinogenesismentioning

confidence: 99%

“…With the help of multiple different cytokines including CSF-1, C-C motif chemokine ligand 2 (CCL-2), IL-34, vascular endothelial growth factor A (VEGFA) or C-X-C motif chemokine ligand 12 (CXCL12) produced by cancer cells as they infiltrate the tumor through the vessels (16). They accumulate in the invasive tumor edge, cancer cell/stromal border, central tumor mass, hypoxic/necrotic regions and perivascular areas (16). TAMs have features of a trophic macrophage phenotype (M2), which means that they may remodel the extracellular matrix and suppress the immune system (8,14,17).…”

Section: Macrophages-general Function In Carcinogenesismentioning

confidence: 99%

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Macrophages in skin melanoma-the key element in melanomagenesis (Review)

Pieniążek¹,

Matkowski

Donizy

2018

Oncol Lett

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Abstract. Cutaneous melanoma is an aggressive cancer and its onset and growth are associated, through direct and indirect interactions, with the cancer microenvironment. The microenvironment comprises a dynamic complex of numerous types of cells (due to histogenesis) that constantly interact with each other through multiple cytokines and signaling proteins. Macrophages are one of the most thoroughly studied pleiotropic cells of the immune system. One of their major cytophysiological functions is their involvement in phagocytosis. Previous studies examining the microenvironment of melanomas and tumor-associated macrophages have revealed that they are involved in all stages of melanomagenesis. In the case of cancer initiation, they form an inflammatory microenvironment and then suppress the anticancer activity of the immune system, stimulate angiogenesis, enhance migration and invasion of the cancer cells, and ultimately contribute to the metastatic process. The present review provides a detailed overview on the function of macrophages in the melanoma microenvironment. IntroductionMelanomas are a rare but aggressive cutaneous type of cancer in humans (1). At the dissemination stage in a majority of cases, the disease is resistant to treatment with cytostatics and radiotherapy (1). Therefore, the identification of novel molecular mechanisms involved in the melanomagenesis process and tumor progression have enabled the production of targeted therapies that yield notable effects (1). The basis for melanomagenesis is the accumulation of genetic disorders in the melanocyte (the most frequent ones include the following mutations: B-Raf proto-oncogene, serine/threonine kinase, N-Ras proto-oncogene, GTPase and phosphatase and tensin homolog) (1). However, only the interaction between microenvironment elements and genetic changes in the melanocyte result in the ultimate transformation of a dysplastic melanocyte into a melanoma cell, and at further stages result in the local invasion and dissemination of the primary lesion (1). It is the microenvironment that is one of the key elements of cancer formation and is being studied at present.A melanoma microenvironment is a markedly heterogenic population of cells that involves fibroblasts, macrophages, lymphocytes, other immune system cells, adipocytes and cells that form the structural elements of cutaneous blood vessels sunk in the extracellular matrix (2). The aforementioned complex network of cellular associations are constantly interacting through direct contact and active protein substances including secretory proteins (e.g., metalloproteinases or

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Dual‐Targeted Engineered Bacterial Outer Membrane Vesicles for Hepatocellular Carcinoma Immunotherapy

Li,

Zhu,

Chen

et al. 2024

Adv Funct Materials

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Cluster of differentiation 47 (CD47) is an important innate immune checkpoint that empowers tumors to send “don't eat me” signals, leading to immune escape. CD47 monoclonal antibodies have achieved remarkable therapeutic success in hematological malignancies. However, their efficacy in solid tumors is limited, mainly because of immunosuppression in the tumor microenvironment. In addition, hematotoxicity severely hinders the clinical translation of CD47 antibodies. Here, a novel genetically programmed nanovesicle, OMV‐CD47/GPC3, is generated for hepatocellular carcinoma (HCC) immunotherapy by fusing anti‐CD47 nanobodies and anti‐GPC3 scFv onto bacterial outer membrane vesicles (OMVs). Following intravenous administration, dual‐targeted OMV‐CD47/GPC3 specifically recognized tumor cells expressing both CD47 and GPC3, thereby actively targeting and accumulating at the orthotopic HCC tumor site without hematotoxicity. OMV‐CD47/GPC3 potently blocked tumor CD47 and promoted macrophage phagocytosis. More importantly, immunogenic OMV‐CD47/GPC3 can effectively remodel the tumor immune microenvironment of orthotopic HCC, especially reprogram tumor‐associated macrophages (TAMs) to the M1‐phenotype and promote dendritic cell maturation, synergistically inducing a robust CD8+ T cell‐mediated anti‐tumor immune response. With the two‐pronged approach of immune checkpoint inhibition and immune activation, engineered OMV‐CD47/GPC3 significantly suppressed orthotopic HCC growth and prevented tumor recurrence and metastasis, thus providing a promising strategy for HCC immunotherapy.

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The Multifaceted Role of Perivascular Macrophages in Tumors

Cited by 216 publications

References 85 publications

S100A4 promotes colon inflammation and colitis-associated colon tumorigenesis

S100A4 promotes colon inflammation and colitis-associated colon tumorigenesis

Macrophages in skin melanoma-the key element in melanomagenesis (Review)

Dual‐Targeted Engineered Bacterial Outer Membrane Vesicles for Hepatocellular Carcinoma Immunotherapy

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