Mast Cells In Cancer Research Articles

Few, but Efficient: The Role of Mast Cells in Breast Cancer and Other Solid Tumors.

Tumor outcome is determined not only by cancer cell-intrinsic features but also by the interaction between cancer cells and their microenvironment. There is great interest in tumor-infiltrating immune cells, yet mast cells have been less studied. Recent work has highlighted the impact of mast cells on the features and aggressiveness of cancer cells, but the eventual effect of mast cell infiltration is still controversial. Here, we review multifaceted findings regarding the role of mast cells in cancer, with a particular focus on breast cancer, which is further complicated because of its classification into subtypes characterized by different biological features, outcome, and therapeutic strategies.

Does a polarization state exist for mast cells in cancer?

The data of literature are discordant about the role of mast cells in different types of neoplasms. In this paper the authors propose the hypothesis that tumor-associated mast cells may switch to different polarization states, conditioning the immunogenic capacities of the different neoplasms. Anti-inflammatory polarized mast cells should express cytokines such as interleukin-10 (IL-10) and then mast cells number should be inversely related to the intensity of inflammatory infiltrate. On the contrary, when mast cells do not express anti-inflammatory cytokines their number should be directly related to the intensity of the inflammatory infiltrate. In this paper we briefly argue around feasible approaches, based on the retrospective studies of tumor tissue samples from neoplasms considered “immunologically hot” and neoplasms considered “immunologically cold”, through immunohistochemistry and immunofluorescence techniques (confocal microscopy). The establishment of the actual existence of a polarization interchange of mast cells, could lead to a new vision in prognostic terms, useful to contrive new approaches in immunotherapy of tumors.

A transcriptomic insight into the impacts of mast cells in lung, breast, and colon cancers

ABSTRACTTo date, the exact impact of mast cells in tumor microenvironment is still controversial because of inconsistency in observations regarding the relationship between mast cell infiltrates and cancer development and prognosis. The discrepancies in previous studies have motivated us to examine the roles of mast cells in cancer pathology from different perspectives. Here, we investigated the impact of mast cells on transcriptomic profiles in the tissue microenvironment. Mice carrying the W-sh mutation in c-kit (KitW-sh) are deficient in mast cell production and were used to assess the influence of mast cells on gene expression. By examining the transcriptomic profile among wild-type mice, KitW-sh mice, and KitW-sh mice with mast cell engraftment, we identified a list of “mast cell–dependent genes,” which are enriched for cancer-related pathways. Utilizing whole-genome gene expression data from both mouse models and human cancer patients, we demonstrated that the expression profile of the mast cell–dependent genes differs between tumor and normal tissues from lung, breast, and colon, respectively. Mast cell infiltration is potentially increased in tumors compared with normal tissues, suggesting that mast cells might participate in tumor development. Accordingly, a prognostic molecular signature was developed based on the mast cell–dependent genes, which predicted recurrence-free survival for human patients with lung, breast, and colon cancers, respectively. Our study provides a novel transcriptomic insight into the impact of mast cells in the tumor microenvironment, though further experimental investigation is needed to validate the exact role of individual mast cell–dependent genes in different cancers.

The role of mast cells in cancers.

Mast cells are immune cells that accumulate in the tumors and their microenvironment during disease progression. Mast cells are armed with a wide array of receptors that sense environment modifications and, upon stimulation, they are able to secrete several biologically active factors involved in the modulation of tumor growth. For example, mast cells are able to secrete pro-angiogenic and growth factors but also pro- and anti-inflammatory mediators. Recent studies have allowed substantial progress in understanding the role of mast cells in tumorigenesis/disease progression but further studies are necessary to completely elucidate their impact in the pathophysiology of cancer. Here we review observations suggesting that mast cells could modulate tumor growth in humans. We also discuss the drawbacks related to observations from mast cell-deficient mouse models, which could have consequences in the determination of a potential causative relationship between mast cells and cancer. We believe that the understanding of the precise role of mast cells in tumor development and progression will be of critical importance for the development of new targeted therapies in human cancers.

Methods for the study of mast cells in cancer.

Tumor growth requires interactions of tumor cells with a receptive and inductive microenvironment. Two major populations of tumor-infiltrating cells are considered to be essential for producing such a microenvironment: (1) proinflammatory cells that nurture the tumor with growth factors and facilitate invasion and metastasis by secreting proteases and (2) immune suppressive leukocytes including T-regulatory cells (Treg) that hinder tumor-specific CD8 T-cell responses, which otherwise could potentially reject the tumor. Among the proinflammatory cells, accumulation of mast cells (MCs) in human tumors is frequently recorded and was recently linked with poor prognosis. Causative links between mast cell infiltration and tumor progression can be deduced from animal studies. There is an interesting link between mast cells and Treg. The adoptive transfer of Treg from healthy syngeneic mice to mice susceptible to colon cancer suppresses focal mastocytosis and hinders tumor progression. Furthermore, T-cell-deficient mice susceptible to colon cancer show enhanced focal mastocytosis and tumor invasion. Here, we describe methods to assess MCs in mouse models of cancer and to investigate how MCs affect tumor epithelium. Additionally, we will detail methods used to investigate how T cells influence MCs and how MCs influence T cells.

Abstract 3659: Mast cell interactions with T-regulatory cells determine the outcome of colon cancer

Abstract Mast cells (MCs) are a bone marrow-derived, long-lived, heterogeneous cellular population that act both as positive and negative regulators of immune responses. They are arguably the biggest chemical factory in the body, and influence other cells through both soluble mediators and cell to cell interaction. MCs are commonly seen in various tumors and have been attributed alternatively with tumor rejection or promotion properties. Tumor infiltrating MCs are derived both from sentinel resident MC progenitors as well as from recruited progenitor cells (1). MC directly influence tumor cell proliferation and invasion (2, 3), but also help shape the tumor microenvironment (1) and modulate immune responses to tumors. Best known for orchestrating inflammation and angiogenesis, the role of MCs in modulating adaptive immune responses has only recently attracted attention. MCs are responsible for expansion of lymph nodes, and recruitment of dendritic cells. MC mediate immune suppression by Treg but can also reverse suppressive properties of Treg (4) or convert Treg into TH17 pro-inflammatory cells The central role of MC in the control of innate and adaptive immunity endows them with the ability to tune the nature of host responses to cancer and ultimately determine the outcome of disease and fate of the cancer patient (5) (6). 1. Maltby S, Khazaie K, McNagny KM. Mast cells in tumor growth: Angiogenesis, tissue remodelling and immune-modulation. Biochim Biophys Acta. 2009;1796(1):19-26. PMCID: 2731828. 2. Strouch MJ, Cheon EC, Salabat MR, Krantz SB, Gounaris E, Melstrom LG, et al. Crosstalk between mast cells and pancreatic cancer cells contributes to pancreatic tumor progression. Clin Cancer Res. 2010;16(8):2257-65. 3. Cheon EC, Khazaie K, Khan MW, Strouch MJ, Krantz SB, Phillips J, et al. Mast cell 5-Lipoxygenase activity promotes intestinal polyposis in APCΔ468 mice. Cancer Research. 2010;(in press). 4. Gounaris E, Blatner NR, Dennis K, Magnusson F, Gurish MF, Strom TB, et al. T-regulatory cells shift from a protective anti-inflammatory to a cancer-promoting proinflammatory phenotype in polyposis. Cancer Res. 2009;69(13):5490-7. 5. Blatner NR, Bonertz A, Beckhove P, Cheon EC, Krantz SB, Strouch M, et al. In colorectal cancer mast cells contribute to systemic regulatory T-cell dysfunction. Proc Natl Acad Sci U S A. 2010;107(14):6430-5. PMCID: 2851977. 6. Colombo MP, Piconese S. Polyps Wrap Mast Cells and Treg within Tumorigenic Tentacles. Cancer Res. 2009. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3659. doi:10.1158/1538-7445.AM2011-3659

The significant role of mast cells in cancer

Mast cells (MC) are a bone marrow-derived, long-lived, heterogeneous cellular population that function both as positive and negative regulators of immune responses. They are arguably the most productive chemical factory in the body and influence other cells through both soluble mediators and cell-to-cell interaction. MC are commonly seen in various tumors and have been attributed alternatively with tumor rejection or tumor promotion. Tumor-infiltrating MC are derived both from sentinel and recruited progenitor cells. MC can directly influence tumor cell proliferation and invasion but also help tumors indirectly by organizing its microenvironment and modulating immune responses to tumor cells. Best known for orchestrating inflammation and angiogenesis, the role of MC in shaping adaptive immune responses has become a focus of recent investigations. MC mobilize T cells and antigen-presenting dendritic cells. They function as intermediaries in regulatory T cells (Treg)-induced tolerance but can also modify or reverse Treg-suppressive properties. The central role of MC in the control of innate and adaptive immunity endows them with the ability to tune the nature of host responses to cancer and ultimately influence the outcome of disease and fate of the cancer patient.

The complexity of the complicity of mast cells in cancer

Mast cells are evolutionarly ancient cells of the immune cells which can secrete a variety of effector molecules. Animal and pathologic studies suggest that mast cells may promote tumor growth in some cancer types but may act in an opposite manner in others. In several mouse models a critical role of mast cells for tumor promotion was demonstrated. In humans mast cells are dependent upon the tyrosine kinase receptor c-Kit. This receptor is inhibited by many of the new anti-cancer tyrosine kinase inhibitors including Pazopanib, Imatinib and Masitinib. These drugs probably ablate some tumor mast cells, in addition to their other known antitumor effects. Understanding the complex roles of mast cells in cancer should aid in understanding mechanisms of current tyrosine kinase inhibitors, and the development of innovative anti-cancer therapies.