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...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2022-06-01
|
Series: | Cells |
Subjects: | |
Online Access: | https://www.mdpi.com/2073-4409/11/13/2027 |
_version_ | 1797480572599140352 |
---|---|
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. |
first_indexed | 2024-03-09T22:02:00Z |
format | Article |
id | doaj.art-d44e2ac2d3e24f7d901c20048133a30d |
institution | Directory Open Access Journal |
issn | 2073-4409 |
language | English |
last_indexed | 2024-03-09T22:02:00Z |
publishDate | 2022-06-01 |
publisher | MDPI AG |
record_format | Article |
series | Cells |
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 |
work_keys_str_mv | AT qunwang ccl22polarizedtamstom2amacrophagesincervicalcancerinvitromodel AT kritikasudan ccl22polarizedtamstom2amacrophagesincervicalcancerinvitromodel AT elisaschmoeckel ccl22polarizedtamstom2amacrophagesincervicalcancerinvitromodel AT berndpeterkost ccl22polarizedtamstom2amacrophagesincervicalcancerinvitromodel AT christinakuhn ccl22polarizedtamstom2amacrophagesincervicalcancerinvitromodel AT aureliavattai ccl22polarizedtamstom2amacrophagesincervicalcancerinvitromodel AT theresavilsmaier ccl22polarizedtamstom2amacrophagesincervicalcancerinvitromodel AT svenmahner ccl22polarizedtamstom2amacrophagesincervicalcancerinvitromodel AT udojeschke ccl22polarizedtamstom2amacrophagesincervicalcancerinvitromodel AT helenehildegardheidegger ccl22polarizedtamstom2amacrophagesincervicalcancerinvitromodel |