Is There a Role for Basophils in Cancer?

Marone, Giancarlo; Schroeder, John T.; Mattei, Fabrizio; Loffredo, Stefania; Gambardella, Adriana; Poto, Remo; Paulis, Amato de; Schiavoni, Giovanna; Varricchi, Gilda

doi:10.3389/fimmu.2020.02103

Cited by 40 publications

(50 citation statements)

References 228 publications

(371 reference statements)

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“…A similar function may be potentially played by ILC2, mast cells and basophils. Although relatively rare in human cancers, these cells can release several soluble mediators that may orchestrate tumor immunity in various manners (11,47,56,71,72,82). For example, following stimulation with IL-33, eosinophils and FIGURE 1 | Anti-tumoral mechanisms of interleukin-33 (IL-33) in the tumor microenvironment (TME).…”

Section: Discussionmentioning

confidence: 99%

Anti-Tumorigenic Activities of IL-33: A Mechanistic Insight

et al. 2020

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Interleukin-33 (IL-33) is an epithelial-derived cytokine that can be released upon tissue damage, stress, or infection, acting as an alarmin for the immune system. IL-33 has long been studied in the context of Th2-related immunopathologies, such as allergic diseases and parasitic infections. However, its capacity to stimulate also Th1-type of immune responses is now well established. IL-33 binds to its specific receptor ST2 expressed by most immune cell populations, modulating a variety of responses. In cancer immunity, IL-33 can display both pro-tumoral and anti-tumoral functions, depending on the specific microenvironment. Recent findings indicate that IL-33 can effectively stimulate immune effector cells (NK and CD8+ T cells), eosinophils, basophils and type 2 innate lymphoid cells (ILC2) promoting direct and indirect anti-tumoral activities. In this review, we summarize the most recent advances on anti-tumor immune mechanisms operated by IL-33, including the modulation of immune checkpoint molecules, with the aim to understand its potential as a therapeutic target in cancer.

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Section: Discussionmentioning

confidence: 99%

Anti-Tumorigenic Activities of IL-33: A Mechanistic Insight

et al. 2020

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“…Recently, Marone et al reported that IL-33-stimulated basophils increased the expression of degranulation marker (CD63) and of granzyme B, resulting in the killing of melanoma tumor cells in vitro [197]. Although the role of IL-33 in regulating basophils in anti-cancer immunity is poorly characterized [198], these findings may widen the scope of effector immune cells in TME activated by IL-33.…”

Section: Basophilsmentioning

confidence: 99%

The Janus Face of IL-33 Signaling in Tumor Development and Immune Escape

Choi

Sosman

Zhang

2021

Cancers

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Interleukin-33 (IL-33), a member of the IL-1 cytokine family, plays a critical role in maintaining tissue homeostasis as well as pathological conditions, such as allergy, infectious disease, and cancer, by promoting type 1 and 2 immune responses. Through its specific receptor ST2, IL-33 exerts multifaceted functions through the activation of diverse intracellular signaling pathways. ST2 is expressed in different types of immune cells, including Th2 cells, Th1 cells, CD8+ T cells, regulatory T cells (Treg), cytotoxic NK cells, group 2 innate lymphoid cells (ILC2s), and myeloid cells. During cancer initiation and progression, the aberrant regulation of the IL-33/ST2 axis in the tumor microenvironment (TME) extrinsically and intrinsically mediates immune editing via modulation of both innate and adaptive immune cell components. The summarized results in this review suggest that IL-33 exerts dual-functioning, pro- as well as anti-tumorigenic effects depending on the tumor type, expression levels, cellular context, and cytokine milieu. A better understanding of the distinct roles of IL-33 in epithelial, stromal, and immune cell compartments will benefit the development of a targeting strategy for this IL-33/ST2 axis for cancer immunotherapy.

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“…Activation of human basophils induces the release of proinflammatory mediators (histamine and cysteinyl leukotriene C 4 ) and the de novo synthesis of several cytokines (IL-4, IL-13, IL-3, CXCL8) [282][283][284] and angiogenic factors [285]. Although increasing evidence indicates that basophils and their mediators are involved in different cancers [286,287], the presence of ECS in these cells is presently unknown. Table 1 summarizes some main effects of cannabinoids and CB receptor ligands on cells of innate and adaptive immune system.…”

Section: The Endocannabinoid System As Gate-keeper Of the Immune Systemmentioning

confidence: 99%

“…Cells of the innate and adaptive immune system play a central role in the initiation and progression of cancer [ 123 , 163 , 190 , 210 , 211 , 286 , 287 ]. Cannabinoids can modulate a variety of biological effects which are central to tumor growth [ 4 , 81 , 297 , 298 ].…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

The Interplay between the Immune and the Endocannabinoid Systems in Cancer

Braile

Marcella

Marone

et al. 2021

Cells

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The therapeutic potential of Cannabis sativa has been recognized since ancient times. Phytocannabinoids, endocannabinoids and synthetic cannabinoids activate two major G protein-coupled receptors, subtype 1 and 2 (CB1 and CB2). Cannabinoids (CBs) modulate several aspects of cancer cells, such as apoptosis, autophagy, proliferation, migration, epithelial-to-mesenchymal transition and stemness. Moreover, agonists of CB1 and CB2 receptors inhibit angiogenesis and lymphangiogenesis in vitro and in vivo. Low-grade inflammation is a hallmark of cancer in the tumor microenvironment (TME), which contains a plethora of innate and adaptive immune cells. These cells play a central role in tumor initiation and growth and the formation of metastasis. CB2 and, to a lesser extent, CB1 receptors are expressed on a variety of immune cells present in TME (e.g., T cells, macrophages, mast cells, neutrophils, NK cells, dendritic cells, monocytes, eosinophils). The activation of CB receptors modulates a variety of biological effects on cells of the adaptive and innate immune system. The expression of CB2 and CB1 on different subsets of immune cells in TME and hence in tumor development is incompletely characterized. The recent characterization of the human cannabinoid receptor CB2-Gi signaling complex will likely aid to design potent and specific CB2/CB1 ligands with therapeutic potential in cancer.

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Is There a Role for Basophils in Cancer?

Cited by 40 publications

References 228 publications

Anti-Tumorigenic Activities of IL-33: A Mechanistic Insight

Anti-Tumorigenic Activities of IL-33: A Mechanistic Insight

The Janus Face of IL-33 Signaling in Tumor Development and Immune Escape

The Interplay between the Immune and the Endocannabinoid Systems in Cancer

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