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Basophils in Tumor Microenvironment and Surroundings

  • Giancarlo Marone
  • Adriana Rosa Gambardella
  • Fabrizio Mattei
  • Jacopo Mancini
  • Giovanna SchiavoniEmail author
  • Gilda Varricchi
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1224)

Abstract

Basophils represent approximately 1% of human peripheral blood leukocytes. Their effector functions were initially appreciated in the 1970s when basophils were shown to express the high-affinity receptor (FcεRI) for IgE and to release proinflammatory mediators (histamine and cysteinyl leukotriene C4) and immunoregulatory cytokines (i.e., IL-4 and IL-13). Basophils in the mouse were subsequently identified and immunologically characterized. There are many similarities but also several differences between human and mouse basophils. Basophil-deficient mice have enabled to examine the in vivo roles of basophils in several immune disorders and, more recently, in tumor immunity. Activated human basophils release several proangiogenic molecules such as vascular endothelial growth factor-A (VEGF-A), vascular endothelial growth factor-B (VEGF-B), CXCL8, angiopoietin 1 (ANGPT1), and hepatocyte growth factor (HGF). On the other side, basophils can exert anti-tumorigenic effects by releasing granzyme B, TNF-α, and histamine. Circulating basophils have been associated with certain human hematologic (i.e., chronic myeloid leukemia) and solid tumors. Basophils have been found in tumor microenvironment (TME) of human lung adenocarcinoma and pancreatic cancer. Basophils played a role in melanoma rejection in basophil-deficient mouse model. By contrast, basophils appear to play a pro-tumorigenic role in experimental and human pancreatic cancer. In conclusion, the roles of basophils in experimental and human cancers have been little investigated and remain largely unknown. The elucidation of the roles of basophils in tumor immunity will demand studies on increasing complexity beyond those assessing basophil density and their microlocalization in TME. There are several fundamental questions to be addressed in experimental models and clinical studies before we understand whether basophils are an ally, adversary, or even innocent bystanders in cancers.

Keywords

Angiopoietins Antigen-presenting cell Basophil Chemokines Cytokines Granzyme Hepatocyte growth factor IL-4 IL-13 Lung cancer Melanoma Pancreatic cancer Tumor immunity Tumor microenvironment Vascular endothelial growth factor 

Abbreviations

ANGPTs

Angiopoietins

APCs

Antigen-presenting cells

BAFF

B-cell-activating factor

BSA

Bovine serum albumin

CAFs

Cancer-associated fibroblasts

CML

Chronic myeloid leukemia

DCs

Dendritic cells

DMBA

7,12-Dimethylbenz(a)athracene

DT

Diphtheria toxin

FcεRI

High-affinity receptor

LTC4

Cysteinyl leukotriene C4

PAF

Platelet-activating factor

PD-1

Programmed cell death-1

PDAC

Pancreatic ductal adenocarcinoma

PD-L1

Programmed death-ligand 1

PGD2

Prostaglandin D2

TDLNs

Tumor-draining lymph nodes

Th2

T helper 2

TME

Tumor microenvironment

Treg

T regulatory cell

TSLP

Thymic stromal lymphopoietin

uPA

Urokinase plasminogen activator

VEGF-A

Vascular endothelial growth factor-A

Notes

Acknowledgments

The authors apologize to the many researchers who have contributed importantly to this field and whose work has not been cited due to space and citation restrictions. The authors thank Dr. Gjada Criscuolo for critical reading of the manuscript, scientists from the CISI Laboratory and Schiavoni’s Laboratory not listed as authors for invaluable collaborations to the work reviewed, and medical graphic artist Fabrizio Fiorbianco for preparing Figs. 2.1 and 2.3. This work was supported in part by grants from the CISI-Lab Project (University of Naples Federico II), the CRèME Project, and the TIMING Project (Regione Campania) to G.V. and from AIRC IG 21366 to G.S.

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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Department of Public HealthUniversity of Naples Federico IINaplesItaly
  2. 2.Azienda Ospedaliera dei Colli-Monaldi Hospital PharmacyNaplesItaly
  3. 3.Department of Oncology and Molecular MedicineIstituto Superiore di SanitàRomeItaly
  4. 4.Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI)University of Naples Federico IINaplesItaly
  5. 5.WAO Center of ExcellenceNaplesItaly
  6. 6.Institute of Experimental Endocrinology and Oncology “G. Salvatore” (IEOS)National Research Council (CNR)NaplesItaly

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