Eosinophils in the Tumor Microenvironment

Mattei, Fabrizio; Andreone, Sara; Marone, Giancarlo; Gambardella, Adriana; Loffredo, Stefania; Varricchi, Gilda; Schiavoni, Giovanna

doi:10.1007/978-3-030-49270-0_1

Cited by 28 publications

(27 citation statements)

References 212 publications

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“…The association between eosinophils and cancer was described more than 100 years ago, and both protumoral and antitumoral activity have been described ( Figure 2 ) [ 32 , 33 ]. Mechanisms behind their accumulation into the blood stream or tumor are uncertain.…”

Section: Eosinophils and Cancermentioning

confidence: 99%

Immunity and Breast Cancer: Focus on Eosinophils

Poncin¹,

Onesti

Josse

et al. 2021

Biomedicines

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The role of eosinophils, a cell type involved in the immune response to parasitic infections and allergies, has been investigated in different cancer types, in both tumor tissue and at the circulating level. Most studies showed a role mainly in conjunction with immunotherapy in melanomas and lung tumors, while few data are available in breast cancer. In this review, we summarize literature data on breast cancer, showing a prognostic role of circulating eosinophil counts as well as of the presence of tumor tissue infiltration by eosinophils. In particular, some studies showed an association between a higher circulating eosinophil count and a good prognosis, as well as an association with response to neoadjuvant chemotherapy in hormone receptor-negative/HER2-positive and in triple negative breast cancer. Several mechanistic studies have also been conducted in in vivo models, but the exact mechanism by which eosinophils act in the presence of breast cancer is still unknown. Further studies on this subject are desirable, in order to understand their role at the cellular level, identify related biomarkers and/or possibly search for new therapeutic targets.

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Section: Eosinophils and Cancermentioning

confidence: 99%

Immunity and Breast Cancer: Focus on Eosinophils

Poncin¹,

Onesti

Josse

et al. 2021

Biomedicines

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“…It stimulates the proliferation of macrophage, granulocyte, erythroid, eosinophil, megakaryocyte and multipotent progenitors cells depending on its concentration ( 28 ). It also controls eosinophil function in some cases ( 29 , 30 ). Fever was the most common adverse effect in sequential administration period of interleukin-2 and GM-CSF.…”

Section: Discussionmentioning

confidence: 99%

“…To our knowledge, tumor-infiltrating eosinophils was firstly described in human gastric cancers in the 1980s. The infiltrating of eosinophils suggests a good prognostic value for prolonged survival ( 30 ). Eosinophils exert anti-tumor effects via direct and indirect mechanisms ( 34 ).…”

Section: Discussionmentioning

confidence: 99%

AGIG Chemo-Immunotherapy in Patients With Advanced Pancreatic Cancer: A Single-Arm, Single-Center, Phase 2 Study

Dai

Qiu

et al. 2021

Front. Oncol.

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BackgroundTo date, chemotherapy remains the only effective treatment of unresectable pancreatic adenocarcinoma. In the past few years, the interest in immunological anticancer therapy rises sharply. AGIG is a novel chemo-immunotherapy regimen that combines nab-paclitaxel + gemcitabine chemotherapy with sequential recombinant interleukin-2 (IL-2) and granulocyte-macrophage colony stimulating factor (GM-CSF) therapy. We conducted a single-arm prospective phase II study to determine the efficacy and safety of the first-line treatment of advanced pancreatic cancer with AGIG regimen.MethodsNab-paclitaxel (125 mg/m2) and gemcitabine (1000 mg/m2) were administered intravenously to all patients on days 1 and 8 triweekly, interleukin-2 (1000000U) and GM-CSF (100 µg) were administered subcutaneously on days 3-5 after chemotherapy. The primary end point was ORR by the Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary end points included safety profile, progression-free survival (PFS), overall survival (OS). Patients’ conditions along with the efficacy and safety were assessed every two cycles.ResultsBetween 11/2018 and 01/2020, sixty-four patients were enrolled. In the sixty-four evaluable patients, the disease control rate (DCR) and overall response rate (ORR) were 76.6% and 43.75%, respectively. The median follow-up time was 12.1 (range 7.1–22.4) months. The median PFS was 5.7 (range 1.63–15.8) months. The median OS was 14.2 (range 2.9–22.0) months. The most common adverse event was fever (75%). The incidence of III/IV grade neutropenia was 4.69%. In subgroup analyses, we found that eosinophil count in the blood elevated three times higher than baseline level predicted a longer survival.ConclusionsThe AGIG chemo-immunotherapy regimen has presented favorable ORR, OS, and manageable toxicities as first-line therapeutic strategy of advanced pancreatic cancer treatment. This regimen may be a novel reliable therapeutic option for patients with preserved performance status. The improvement of treatment efficiency may be related to the activation of non-specific immune response.Clinical Trial Registrationhttps://clinicaltrials.gov/. identifier NCT03768687.

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“…Eosinophils. Eosinophils are involved in parasitic infections, allergies and cancer [ 271 , 272 , 273 ]. Eosinophils express only the CB2 receptor [ 274 ].…”

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

confidence: 99%

“…More recently, it has been confirmed that human and mouse eosinophils selectively express the CB2 receptor [ 277 ]. Although the pro- and anti-tumorigenic effects of eosinophils are well known [ 273 , 278 , 279 ], there are still no studies on the contribution of endocannabinoid-eosinophil interactions in TME.…”

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

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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Eosinophils in the Tumor Microenvironment

Cited by 28 publications

References 212 publications

Immunity and Breast Cancer: Focus on Eosinophils

Immunity and Breast Cancer: Focus on Eosinophils

AGIG Chemo-Immunotherapy in Patients With Advanced Pancreatic Cancer: A Single-Arm, Single-Center, Phase 2 Study

The Interplay between the Immune and the Endocannabinoid Systems in Cancer

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