A role of eosinophils in mediating the anti-tumour effect of cryo-thermal treatment

Jia, Shengguo; Li, Wentao; Liu, Ping; Xu, Lisa X.

doi:10.1038/s41598-019-49734-5

Cited by 17 publications

(15 citation statements)

References 59 publications

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“…Despite several reports highlighting the influence of eosinophils on the nature of immune cell infiltrates in various solid tumor models, 12 , 25 , 48 , 49 we observed that IL-33-induced changes in the microenvironment of the CT26 tumors only occurred in CD4 + T cells and Tregs but not M1 macrophages, myeloid derived suppressor cells (MDSCs), CD8 + T or NK cells. In accordance with other studies, 18 , 19 Tregs slightly increased in CT26 tumors post-IL-33 treatment but this increase was not associated with a higher tumor burden.…”

Section: Discussioncontrasting

confidence: 88%

“…Our observation that IL-33 can drive IL-5 and CCL24 expression is also supported by another study describing that in eosinophilia of airway inflammation, IL-33stimulated production of IL-5 is accompanied by increased levels of CCL24, but not of CCL11. 47 Despite several reports highlighting the influence of eosinophils on the nature of immune cell infiltrates in various solid tumor models, 12,25,48,49 we observed that IL-33-induced changes in the microenvironment of the CT26 tumors only occurred in CD4 + T cells and Tregs but not M1 macrophages, myeloid derived suppressor cells (MDSCs), CD8 + T or NK cells. In accordance with other studies, 18,19 Tregs slightly increased in CT26 tumors post-IL-33 treatment but this increase was not associated with a higher tumor burden.…”

Section: Discussioncontrasting

confidence: 60%

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IL-33 reduces tumor growth in models of colorectal cancer with the help of eosinophils

et al. 2020

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In many types of cancer, presence of eosinophils in tumors correlate with an improved disease outcome. In line with this, activated eosinophils have been shown to reduce tumor growth in colorectal cancer (CRC). Interleukin (IL)-33 has recently emerged as a cytokine that is able to inhibit the development of tumors through eosinophils and other cells of the tumor microenvironment thereby positively influencing disease progress. Here, we asked whether eosinophils are involved in the effects of IL-33 on tumor growth in CRC. In models of CT26 cell engraftment and colitis-associated CRC, tumor growth was reduced after IL-33 treatment. The growth reduction was absent in eosinophil-deficient ΔdblGATA-1 mice but was restored by adoptive transfer of ex vivo-activated eosinophils indicating that the antitumor effect of IL-33 depends on the presence of eosinophils. In vitro, IL-33 increased the expression of markers of activation and homing in eosinophils, such as CD11b and Siglec-F, and the degranulation markers CD63 and CD107a. Increased expression of Siglec-F, CD11b and CD107a was also seen in vivo in eosinophils after IL-33 treatment. Viability and cytotoxic potential of eosinophils and their migration properties toward CCL24 were enhanced indicating direct effects of IL-33 on eosinophils. IL-33 treatment led to increased levels of IL-5 and CCL24 in tumors. Our data show that the presence of eosinophils is mandatory for IL-33-induced tumor reduction in models of CRC and that the mechanisms include eosinophil recruitment, activation and degranulation. Our findings also emphasize the potential use of IL-33 as an adjuvants in CRC immunotherapy.

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Section: Discussioncontrasting

confidence: 88%

Section: Discussioncontrasting

confidence: 60%

IL-33 reduces tumor growth in models of colorectal cancer with the help of eosinophils

et al. 2020

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“…A similar response shared by Siglec‐8 and Siglec‐F is that both get internalized following ligand binding 24–26 . This makes it potentially problematic, without proper gating strategies and the use of additional eosinophil markers, to use surface expression Siglec‐F to track eosinophils after systemic administration of Siglec‐F antibody, even though this is frequently done 27–30 …”

Section: Introductionmentioning

confidence: 99%

Frontline Science: Superior mouse eosinophil depletion in vivo targeting transgenic Siglec-8 instead of endogenous Siglec-F: Mechanisms and pitfalls

Knuplez

Krier-Burris

Cao

et al. 2020

Journal of Leukocyte Biology

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Eosinophils are important multifunctional granulocytes. When studying eosinophil function and its contribution to diseases, mouse models are often used. Mouse eosinophils selectively express sialic acid‐binding immunoglobulin‐like lectin (Siglec)‐F. Its closest functional paralog on human eosinophils is Siglec‐8. These Siglecs are being used to target eosinophils when exploring their mechanistic roles in disease and for potential therapeutic benefit. In order to facilitate preclinical studies of human Siglec‐8, we developed transgenic mouse strains expressing human Siglec‐8 only on the surface of eosinophils with or without endogenous Siglec‐F and have begun characterizing various cellular functions in vitro and in vivo. Eosinophils from Siglec‐8+ mice, with or without Siglec‐F, responded to Siglec‐8 antibody engagement in vitro by up‐regulating surface CD11b, whereas Siglec‐F antibody had no such effect. Engagement of Siglec‐F or Siglec‐8 with respective antibodies in vitro resulted in only modest increases in cell death. Administration of rat Siglec‐F antibodies to mice led to a significant decrease in Siglec‐F surface expression on eosinophils due to internalization, and thus appeared to decrease eosinophil numbers based on Siglec‐F+ cells, but with proper gaiting strategies did not in fact result in significant eosinophil depletion. In marked contrast, administration of mouse Siglec‐8 antibodies rapidly and effectively depleted eosinophils from blood and spleens of mice, but an F(ab′)2 version did not, indicating an Fc‐mediated mechanism for eosinophil depletion in vivo. Siglec‐8 expressing mice with or without endogenous Siglec‐F will be useful to study Siglec‐8‐based therapeutics, and may be a preferred approach when acute or chronic eosinophil depletion is needed.

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“…Our previous studies demonstrate that cryo-thermal therapy can not only effectively ablate tumors locally but also induce systematic antitumor immunity [8][9][10]15,17,44,46,47]. After cryo-thermal therapy, tumors in situ release tumor antigens and danger signals, which facilitate a durable antitumor adaptive immune response [15,17,47].…”

Section: Discussionmentioning

confidence: 99%

Iron Released after Cryo-Thermal Therapy Induced M1 Macrophage Polarization, Promoting the Differentiation of CD4+ T Cells into CTLs

Wang

Cheng

Peng

et al. 2021

IJMS

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Macrophages play critical roles in both innate and adaptive immunity and are known for their high plasticity in response to various external signals. Macrophages are involved in regulating systematic iron homeostasis and they sequester iron by phagocytotic activity, which triggers M1 macrophage polarization and typically exerts antitumor effects. We previously developed a novel cryo-thermal therapy that can induce the mass release of tumor antigens and damage-associated molecular patterns (DAMPs), promoting M1 macrophage polarization. However, that study did not examine whether iron released after cryo-thermal therapy induced M1 macrophage polarization; this question still needed to be addressed. We hypothesized that cryo-thermal therapy would cause the release of a large quantity of iron to augment M1 macrophage polarization due to the disruption of tumor cells and blood vessels, which would further enhance antitumor immunity. In this study, we investigated iron released in primary tumors, the level of iron in splenic macrophages after cryo-thermal therapy and the effect of iron on macrophage polarization and CD4+ T cell differentiation in metastatic 4T1 murine mammary carcinoma. We found that a large amount of iron was released after cryo-thermal therapy and could be taken up by splenic macrophages, which further promoted M1 macrophage polarization by inhibiting ERK phosphorylation. Moreover, iron promoted DC maturation, which was possibly mediated by iron-induced M1 macrophages. In addition, iron-induced M1 macrophages and mature DCs promoted the differentiation of CD4+ T cells into the CD4 cytolytic T lymphocytes (CTL) subset and inhibited differentiation into Th2 and Th17 cells. This study explains the role of iron in cryo-thermal therapy-induced antitumor immunity from a new perspective.

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A role of eosinophils in mediating the anti-tumour effect of cryo-thermal treatment

Cited by 17 publications

References 59 publications

IL-33 reduces tumor growth in models of colorectal cancer with the help of eosinophils

IL-33 reduces tumor growth in models of colorectal cancer with the help of eosinophils

Frontline Science: Superior mouse eosinophil depletion in vivo targeting transgenic Siglec-8 instead of endogenous Siglec-F: Mechanisms and pitfalls

Iron Released after Cryo-Thermal Therapy Induced M1 Macrophage Polarization, Promoting the Differentiation of CD4+ T Cells into CTLs

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