Basophil Recruitment into Tumor-Draining Lymph Nodes Correlates with Th2 Inflammation and Reduced Survival in Pancreatic Cancer Patients

Monte, Lucia De; Wörmann, Sonja M.; Brunetto, Emanuela; Heltai, Silvia; Magliacane, Gilda; Reni, Michele; Paganoni, Anna Maria; Recalde, Helios; Mondino, Anna; Falconi, Massimo; Ambrosi, Francesca; Balzano, Gianpaolo; Algül, Hana; Doglioni, Claudio; Protti, Maria Pia

doi:10.1158/0008-5472.can-15-1801-t

Cited by 130 publications

(120 citation statements)

References 49 publications

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“…These mice are profoundly deficient in mast cells and also exhibit several other abnormalities, such as basophil deficiency (181, 182). Recent evidence suggests that basophils can play a role in human pancreatic cancer (183). New Kit-independent mast cell-deficient mice (184) have been used to evaluate the role of mast cells in cutaneous lymphoma (48), malignant pleural effusion (35), and skin cancerogenesis (118).…”

Section: Outstanding Questionsmentioning

confidence: 99%

Are Mast Cells MASTers in Cancer?

et al. 2017

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Prolonged low-grade inflammation or smoldering inflammation is a hallmark of cancer. Mast cells form a heterogeneous population of immune cells with differences in their ultra-structure, morphology, mediator content, and surface receptors. Mast cells are widely distributed throughout all tissues and are stromal components of the inflammatory microenvironment that modulates tumor initiation and development. Although canonically associated with allergic disorders, mast cells are a major source of pro-tumorigenic (e.g., angiogenic and lymphangiogenic factors) and antitumorigenic molecules (e.g., TNF-α and IL-9), depending on the milieu. In certain neoplasias (e.g., gastric, thyroid and Hodgkin’s lymphoma) mast cells play a pro-tumorigenic role, in others (e.g., breast cancer) a protective role, whereas in yet others they are apparently innocent bystanders. These seemingly conflicting results suggest that the role of mast cells and their mediators could be cancer specific. The microlocalization (e.g., peritumoral vs intratumoral) of mast cells is another important aspect in the initiation/progression of solid and hematologic tumors. Increasing evidence in certain experimental models indicates that targeting mast cells and/or their mediators represent a potential therapeutic target in cancer. Thus, mast cells deserve focused consideration also as therapeutic targets in different types of tumors. There are many unanswered questions that should be addressed before we understand whether mast cells are an ally, adversary, or innocent bystanders in human cancers.

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Section: Outstanding Questionsmentioning

confidence: 99%

Are Mast Cells MASTers in Cancer?

et al. 2017

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“…Basophils infiltrate human gastric mucosa of Helicobacter pylori‐ infected patients affected by severe gastritis and cancer . De Monte and collaborators identified IL‐4 + basophils in draining lymph nodes (LN) of patients with pancreatic ductal adenocarcinoma (PDAC) . The presence of basophils in draining LNs was an independent negative prognostic factor of patients' survival after surgery.…”

Section: Role Of Mast Cells and Basophils In Health And Diseasementioning

confidence: 99%

“…Basophils have long been marginalized in immunological studies and they were erroneously regarded as minor relatives of mast cells. Recent advances in analytical tools for basophils have highlighted the non‐redundant roles of basophils not only in allergic inflammation but also in autoimmune disorders, microbial infections, immunodeficiencies, and cancer . In murine models, there is convincing evidence of the heterogeneity of basophils expressing the TSLP receptor or the IL‐3 receptor .…”

Section: Closing Thoughtsmentioning

confidence: 99%

Human mast cells and basophils—How are they similar how are they different?

Varricchi

Raap

Rivellese

et al. 2018

Immunological Reviews

129

116

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Mast cells and basophils are key contributors to allergies and other inflammatory diseases since they are the most prominent source of histamine as well as numerous additional inflammatory mediators which drive inflammatory responses. However, a closer understanding of their precise roles in allergies and other pathological conditions has been marred by the considerable heterogeneity that these cells display, not only between mast cells and basophils themselves but also across different tissue locations and species. While both cell types share the ability to rapidly degranulate and release histamine following high-affinity IgE receptor cross-linking, they differ markedly in their ability to either react to other stimuli, generate inflammatory eicosanoids or release immunomodulating cytokines and chemokines. Furthermore, these cells display considerable pharmacological heterogeneity which has stifled attempts to develop more effective anti-allergic therapies. Mast cell- and basophil-specific transcriptional profiling, at rest and after activation by innate and adaptive stimuli, may help to unravel the degree to which these cells differ and facilitate a clearer understanding of their biological functions and how these could be targeted by new therapies.

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“…Although the physiological role of mast cells and basophils remains enigmatic, there is now increasing evidence that these cells are critically involved not only in allergic disorders but also in autoimmune and infectious diseases, immunodeficiencies, and cancer [13,14,15,17,83], with multifaceted roles due to their ability to mediate both pro- and anti-inflammatory/immunomodulatory responses [21,23,84]. …”

Section: Differential Role Of Human Basophils and Mast Cells In Hiv Imentioning

confidence: 99%

“…Despite some similarities, there are striking differences in the morphological, biochemical, and immunological characteristics of human basophils and mast cells (Table 1) and in their roles played in innate and adaptive immunity [12,13]. Although the primary location of human basophils is the peripheral blood, under certain pathological conditions basophils are recruited into inflamed tissues [14,15,16] and in lymph nodes [17,18]. …”

Section: Introductionmentioning

confidence: 99%

Are Basophils and Mast Cells Masters in HIV Infection?

Marone

Varricchi²,

Loffredo³

et al. 2016

Int Arch Allergy Immunol

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The World Health Organization AIDS epidemic update estimates that more than 37 million people are living with HIV infection. Despite the unprecedented success of antiretroviral treatments, significant challenges remain in the fight against HIV. In particular, how uninfected cells capture HIV and transmit virions to target cells remains an unanswered question. Tissue mast cells and peripheral blood basophils can be exposed to virions or HIV products during infection. Several HIV proteins (i.e., envelope glycoproteins gp120 and gp41, Tat, and Nef) can interact with distinct surface receptors expressed by human basophils and mast cells and modulate their functional responses at different levels. Additionally, several groups have provided evidence that human mast cells can be infected in vitro, as well as in vivo, by certain strains of HIV. Recently, it has been demonstrated that basophils purified from healthy donors and intestinal mast cells can efficiently capture HIV on their cell surface and, cocultured with CD4⁺ T cells, they can transfer the virus to the cocultured cells leading to infection. Direct contact between human basophils or intestinal mast cells and CD4⁺ T cells can mediate viral trans-infection of T cells through the formation of viral synapses. Thus, basophils and mast cells can provide a cellular basis for capturing and then spreading viruses throughout the body. Collectively, these findings suggest that human basophils and mast cells play a complex and possibly distinct role in HIV infection, warranting further investigations.

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Basophil Recruitment into Tumor-Draining Lymph Nodes Correlates with Th2 Inflammation and Reduced Survival in Pancreatic Cancer Patients

Cited by 130 publications

References 49 publications

Are Mast Cells MASTers in Cancer?

Are Mast Cells MASTers in Cancer?

Human mast cells and basophils—How are they similar how are they different?

Are Basophils and Mast Cells Masters in HIV Infection?

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