The Role of Mast Cells in Molding the Tumor Microenvironment

Rigoni, Alice; Colombo, Mario P.; Pucillo, Carlo

doi:10.1007/s12307-014-0152-8

Cited by 64 publications

(58 citation statements)

References 96 publications

(93 reference statements)

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“…These mediators lead to crosstalk with immune cells and tumor cells, and separately contribute to the formation of an immunosuppressive environment, and enhance tumor cell activity. 27 Furthermore, an association of cigarette smoking with a rise of mast cells was observed. 28 Increasing evidence now implies that mast cells promote expression of pro-inflammatory chemokines.…”

Section: Discussionmentioning

confidence: 93%

Smoker and non-smoker lung adenocarcinoma is characterized by distinct tumor immune microenvironments

et al. 2018

OncoImmunology

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Tobacco smoking causes DNA damages in epithelial cells and immune dysfunction in the lung, which collectively contribute to lung carcinogenesis and progression. However, potential mechanisms by which tumor-infiltrating immune cells contribute to lung cancer survival and their differential contributions in ever-smokers and never-smokers are not well studied. Here, we performed integrative analysis of 11 lung cancer gene-expression datasets, including 1,111 lung adenocarcinomas and 200 adjacent normal lung samples. Distinct pathways were altered in lung carcinogenesis in ever-smokers and never-smokers. Never-smoker patients had a better outcome than ever-smoker patients. We characterized compositional patterns of 21 types of immune cells in lung adenocarcinomas and revealed the complex association between immune cell composition and clinical outcomes. Interestingly, we found two subsets of immune cells, mast cells and CD4+ memory T cells, which had completely opposite associations with outcomes in resting and activated status. We further discovered that several chemokines and their associated receptors (e.g., CXCL11-CX3CR1 axis) were selectively altered in lung tumors in response to cigarette smoking and their abundances showed stronger correlation with fractions of these immune subsets in ever-smokers than never-smokers. The status switched from the resting to activated forms in mast cells and CD4+ memory T cells might manifest some important processes induced by cigarette smoking during tumor development and progression. Our findings suggested that aberrant activation of mast cells and CD4+ memory T cells plays crucial roles in cigarette smoking-induced immune dysfunction in the lung, which contributes to tumor development and progression.

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Section: Discussionmentioning

confidence: 93%

Smoker and non-smoker lung adenocarcinoma is characterized by distinct tumor immune microenvironments

et al. 2018

OncoImmunology

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“…Although increased tumoral MC density has been associated with poor prognosis in many studies (n=18) (16), it has also been associated with good prognosis (16) in cancer, such as esophageal SCC (17), breast (18) and colorectal (19). Moreover, murine epidermal tumors became larger and with more metastasis in c-KIT-deficient mice (20).…”

Section: Stromal Cells (Red Arrows) At the Invasive Front Of Carcinmentioning

confidence: 99%

Low Mast Cell Density Predicts Poor Prognosis in Oral Squamous Cell Carcinoma and Reduces Survival in Head and Neck Squamous Cell Carcinoma

Attramadal

Kumar

Gao

et al. 2016

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Abstract. Background: The cellular composition of the tumor microenvironment (TME) at the invading front of oral squamous cell carcinomas (OSCCsThe growth of oral squamous cell carcinoma cells is influenced by its stroma. Stromal cells such as mast cells (MCs), cancer-associated fibroblasts (CAFs), tumorassociated macrophages (TAMs), endothelial cells, pericytes, smooth muscle cells and lymphocytes promote tumor growth, local infiltration, proliferation, neovascularization and escape from immune defense (1). Such cancer-amended stroma is referred to as the tumor microenvironment (TME) (2), and is probably as important as the cancer itself in facilitating cancer cell invasion and metastasis. In the current study of early-stage oral squamous cell carcinomas (OSCCs), we examined the significance of MCs, CAFs, TAMs and endothelial cells in the TME of the invasive front, and their influence on disease recurrence. The MC findings were further explored in a larger cohort of patients with head and neck squamous cell carcinoma.MCs are especially present in surface mucosa such as the skin, bronchial tract, lungs and digestive tract, conjunctiva, nose and mouth, and are best known for their role in allergic immune reactions (3). The TME in OSCC contains more MCs than normal oral mucosa (4), but their role in TME is intricate and poorly understood. These MCs may promote cancer growth by stimulating angiogenesis and tissue remodeling, but also exert anticancerous effects, depending on cofactors and cell location (5).CAFs represent a common functional state of cancerstimulated mesenchymal cells. Their cell of origin is 5499

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“…Macrophages, an important cell component of the tumor stroma, are recruited and mobilized by tumor-derived factors such as IL-4, IFN-γ and IL-13 and then induced to differentiate into pro-tumorigenic tumor-associated macrophages (TAMs). TAMs can promote tumor angiogenesis, proliferation and invasion [1, 2, 5], and TAM infiltration is often associated with poor prognosis. Inhibition of TAM infiltration leads to glioma shrinkage in animal models [6, 7].…”

Section: Introductionmentioning

confidence: 99%

Class A1 scavenger receptor modulates glioma progression by regulating M2-like tumor-associated macrophage polarization

Zhang

Sun

et al. 2016

Oncotarget

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Macrophages enhance glioma development and progression by shaping the tumor microenvironment. Class A1 scavenger receptor (SR-A1), a pattern recognition receptor primarily expressed in macrophages, is up-regulated in many human solid tumors. We found that SR-A1 expression in 136 human gliomas was positively correlated with tumor grade (P<0.01), but not prognosis or tumor recurrence. SR-A1-expressing macrophages originated primarily from circulating monocytes attracted to tumor tissue, and were almost twice as numerous as resident microglia in glioma tissues (P<0.001). The effects of SR-A1 on glioma proliferation and invasion were assessed in vivo using an SR-A1-deficient murine orthotopic glioma model. SR-A1 deletion promoted M2-like tumor-associated macrophage (TAM) polarization in mice by activating STAT3 and STAT6, which resulted in robust orthotopic glioma proliferation and angiogenesis. Finally, we found that HSP70 might be an endogenous ligand that activates SR-A1-dependent anti-tumorigenic pathways in gliomas, although its expression does not appear informative for diagnostic purposes. Our findings demonstrate a relationship between TAMs, SR-A1 expression and glioma growth and provide new insights into the pathogenic role of TAMs in glioma.

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The Role of Mast Cells in Molding the Tumor Microenvironment

Cited by 64 publications

References 96 publications

Smoker and non-smoker lung adenocarcinoma is characterized by distinct tumor immune microenvironments

Smoker and non-smoker lung adenocarcinoma is characterized by distinct tumor immune microenvironments

Low Mast Cell Density Predicts Poor Prognosis in Oral Squamous Cell Carcinoma and Reduces Survival in Head and Neck Squamous Cell Carcinoma

Class A1 scavenger receptor modulates glioma progression by regulating M2-like tumor-associated macrophage polarization

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