CCL22-Polarized TAMs to M2a Macrophages in Cervical Cancer In Vitro Model

Macrophages are dynamic cells susceptible to the local microenvironment which includes tumor-associated macrophages (TAMs) in cancers. TAMs are a collection of heterogeneous macrophages, including M1 and M2 subtypes, shaped by various activation modes and labeled with various markers in different tu...

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Main Authors: Qun Wang, Kritika Sudan, Elisa Schmoeckel, Bernd Peter Kost, Christina Kuhn, Aurelia Vattai, Theresa Vilsmaier, Sven Mahner, Udo Jeschke, Helene Hildegard Heidegger
Format: Article
Language:English
Published: MDPI AG 2022-06-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/11/13/2027
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author Qun Wang
Kritika Sudan
Elisa Schmoeckel
Bernd Peter Kost
Christina Kuhn
Aurelia Vattai
Theresa Vilsmaier
Sven Mahner
Udo Jeschke
Helene Hildegard Heidegger
author_facet Qun Wang
Kritika Sudan
Elisa Schmoeckel
Bernd Peter Kost
Christina Kuhn
Aurelia Vattai
Theresa Vilsmaier
Sven Mahner
Udo Jeschke
Helene Hildegard Heidegger
author_sort Qun Wang
collection DOAJ
description Macrophages are dynamic cells susceptible to the local microenvironment which includes tumor-associated macrophages (TAMs) in cancers. TAMs are a collection of heterogeneous macrophages, including M1 and M2 subtypes, shaped by various activation modes and labeled with various markers in different tumors. CCL22+-infiltrating cells are thought to be significantly associated with the prognosis of cervical cancer patients. Moreover, CCL22 is an established marker of M2a macrophages. Although the phenotypic identification of M1 and M2 macrophages is well established in mice and human macrophages cultured in a medium with fetal calf serum (FCS), fewer studies have focused on M2 subtypes. In addition, the question of whether CCL22 affects polarization of M2a macrophages remains unanswered. This study constructed a co-culture system to shape TAMs in vitro. We found that CCL22 was mainly secreted by TAMs but not cervical cancer cell lines. Human peripheral blood monocytes were differentiated into uncommitted macrophages (M0) and then polarized to M1, M2a, M2b, and M2c macrophages using LPS plus IFNr, IL-4, LPS plus IL1β, and IL-10, respectively. Using flowcytometry, we found CD80++ was the marker of M1 and M2b, CD206++ was the marker of M2a, and CD163++ was the marker of M2c, compared with M0 macrophages. By regulating CCL22, we found that the mean fluorescence intensity (MFI) of CD206 in TAMs was significantly affected compared to the control group. Therefore, CCL22 could polarize TAMs of cervical cancer toward M2a macrophages. In conclusion, our study revealed that CCL22 could be a therapeutic target for cervical cancer, which might be because of its role in regulating macrophage polarization.
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spelling doaj.art-d44e2ac2d3e24f7d901c20048133a30d2023-11-23T19:48:18ZengMDPI AGCells2073-44092022-06-011113202710.3390/cells11132027CCL22-Polarized TAMs to M2a Macrophages in Cervical Cancer In Vitro ModelQun Wang0Kritika Sudan1Elisa Schmoeckel2Bernd Peter Kost3Christina Kuhn4Aurelia Vattai5Theresa Vilsmaier6Sven Mahner7Udo Jeschke8Helene Hildegard Heidegger9Department of Obstetrics and Gynecology, University Hospital, LMU Munich, 80377 Munich, GermanyDepartment of Cardiology, University Hospital Munich, LMU Munich, 81377 Munich, GermanyDepartment of Pathology, LMU Munich, 80377 Munich, GermanyDepartment of Obstetrics and Gynecology, University Hospital, LMU Munich, 80377 Munich, GermanyDepartment of Obstetrics and Gynecology, University Hospital, LMU Munich, 80377 Munich, GermanyDepartment of Obstetrics and Gynecology, University Hospital, LMU Munich, 80377 Munich, GermanyDepartment of Obstetrics and Gynecology, University Hospital, LMU Munich, 80377 Munich, GermanyDepartment of Obstetrics and Gynecology, University Hospital, LMU Munich, 80377 Munich, GermanyDepartment of Obstetrics and Gynecology, University Hospital, LMU Munich, 80377 Munich, GermanyDepartment of Obstetrics and Gynecology, University Hospital, LMU Munich, 80377 Munich, GermanyMacrophages are dynamic cells susceptible to the local microenvironment which includes tumor-associated macrophages (TAMs) in cancers. TAMs are a collection of heterogeneous macrophages, including M1 and M2 subtypes, shaped by various activation modes and labeled with various markers in different tumors. CCL22+-infiltrating cells are thought to be significantly associated with the prognosis of cervical cancer patients. Moreover, CCL22 is an established marker of M2a macrophages. Although the phenotypic identification of M1 and M2 macrophages is well established in mice and human macrophages cultured in a medium with fetal calf serum (FCS), fewer studies have focused on M2 subtypes. In addition, the question of whether CCL22 affects polarization of M2a macrophages remains unanswered. This study constructed a co-culture system to shape TAMs in vitro. We found that CCL22 was mainly secreted by TAMs but not cervical cancer cell lines. Human peripheral blood monocytes were differentiated into uncommitted macrophages (M0) and then polarized to M1, M2a, M2b, and M2c macrophages using LPS plus IFNr, IL-4, LPS plus IL1β, and IL-10, respectively. Using flowcytometry, we found CD80++ was the marker of M1 and M2b, CD206++ was the marker of M2a, and CD163++ was the marker of M2c, compared with M0 macrophages. By regulating CCL22, we found that the mean fluorescence intensity (MFI) of CD206 in TAMs was significantly affected compared to the control group. Therefore, CCL22 could polarize TAMs of cervical cancer toward M2a macrophages. In conclusion, our study revealed that CCL22 could be a therapeutic target for cervical cancer, which might be because of its role in regulating macrophage polarization.https://www.mdpi.com/2073-4409/11/13/2027cervical cancerTAMsCCL22M2a macrophages
spellingShingle Qun Wang
Kritika Sudan
Elisa Schmoeckel
Bernd Peter Kost
Christina Kuhn
Aurelia Vattai
Theresa Vilsmaier
Sven Mahner
Udo Jeschke
Helene Hildegard Heidegger
CCL22-Polarized TAMs to M2a Macrophages in Cervical Cancer In Vitro Model
Cells
cervical cancer
TAMs
CCL22
M2a macrophages
title CCL22-Polarized TAMs to M2a Macrophages in Cervical Cancer In Vitro Model
title_full CCL22-Polarized TAMs to M2a Macrophages in Cervical Cancer In Vitro Model
title_fullStr CCL22-Polarized TAMs to M2a Macrophages in Cervical Cancer In Vitro Model
title_full_unstemmed CCL22-Polarized TAMs to M2a Macrophages in Cervical Cancer In Vitro Model
title_short CCL22-Polarized TAMs to M2a Macrophages in Cervical Cancer In Vitro Model
title_sort ccl22 polarized tams to m2a macrophages in cervical cancer in vitro model
topic cervical cancer
TAMs
CCL22
M2a macrophages
url https://www.mdpi.com/2073-4409/11/13/2027
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