An Ex Vivo 3D Tumor Microenvironment-Mimicry Culture to Study TAM Modulation of Cancer Immunotherapy
Tumor-associated macrophages (TAMs) accumulate in the solid tumor microenvironment (TME) and have been shown to promote tumor growth and dampen antitumor immune responses. TAM-mediated suppression of T-cell antitumor reactivity is considered to be a major obstacle for many immunotherapies, including...
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| Format: | Article |
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MDPI AG
2022-05-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/9/1583 |
| _version_ | 1797505263593324544 |
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| author | Yan-Ruide Li Yanqi Yu Adam Kramer Ryan Hon Matthew Wilson James Brown Lili Yang |
| author_facet | Yan-Ruide Li Yanqi Yu Adam Kramer Ryan Hon Matthew Wilson James Brown Lili Yang |
| author_sort | Yan-Ruide Li |
| collection | DOAJ |
| description | Tumor-associated macrophages (TAMs) accumulate in the solid tumor microenvironment (TME) and have been shown to promote tumor growth and dampen antitumor immune responses. TAM-mediated suppression of T-cell antitumor reactivity is considered to be a major obstacle for many immunotherapies, including immune checkpoint blockade and adoptive T/CAR-T-cell therapies. An ex vivo culture system closely mimicking the TME can greatly facilitate the study of cancer immunotherapies. Here, we report the development of a 3D TME-mimicry culture that is comprised of the three major components of a human TME, including human tumor cells, TAMs, and tumor antigen-specific T cells. This TME-mimicry culture can readout the TAM-mediated suppression of T-cell antitumor reactivity, and therefore can be used to study TAM modulation of T-cell-based cancer immunotherapy. As a proof-of-principle, the studies of a PD-1/PD-L1 blockade therapy and a MAO-A blockade therapy were performed and validated. |
| first_indexed | 2024-03-10T04:16:07Z |
| format | Article |
| id | doaj.art-868aab000c1046e5b29fcd08f9535442 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T04:16:07Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-868aab000c1046e5b29fcd08f95354422023-11-23T08:01:23ZengMDPI AGCells2073-44092022-05-01119158310.3390/cells11091583An Ex Vivo 3D Tumor Microenvironment-Mimicry Culture to Study TAM Modulation of Cancer ImmunotherapyYan-Ruide Li0Yanqi Yu1Adam Kramer2Ryan Hon3Matthew Wilson4James Brown5Lili Yang6Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA 90095, USADepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA 90095, USADepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA 90095, USADepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA 90095, USADepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA 90095, USADepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA 90095, USADepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA 90095, USATumor-associated macrophages (TAMs) accumulate in the solid tumor microenvironment (TME) and have been shown to promote tumor growth and dampen antitumor immune responses. TAM-mediated suppression of T-cell antitumor reactivity is considered to be a major obstacle for many immunotherapies, including immune checkpoint blockade and adoptive T/CAR-T-cell therapies. An ex vivo culture system closely mimicking the TME can greatly facilitate the study of cancer immunotherapies. Here, we report the development of a 3D TME-mimicry culture that is comprised of the three major components of a human TME, including human tumor cells, TAMs, and tumor antigen-specific T cells. This TME-mimicry culture can readout the TAM-mediated suppression of T-cell antitumor reactivity, and therefore can be used to study TAM modulation of T-cell-based cancer immunotherapy. As a proof-of-principle, the studies of a PD-1/PD-L1 blockade therapy and a MAO-A blockade therapy were performed and validated.https://www.mdpi.com/2073-4409/11/9/1583tumor-associated macrophage (TAM)tumor microenvironment (TME)ex vivo 3D TME-mimicry culturechimeric antigen receptor (CAR)CAR-engineered T (CAR-T) cellcancer immunotherapy |
| spellingShingle | Yan-Ruide Li Yanqi Yu Adam Kramer Ryan Hon Matthew Wilson James Brown Lili Yang An Ex Vivo 3D Tumor Microenvironment-Mimicry Culture to Study TAM Modulation of Cancer Immunotherapy Cells tumor-associated macrophage (TAM) tumor microenvironment (TME) ex vivo 3D TME-mimicry culture chimeric antigen receptor (CAR) CAR-engineered T (CAR-T) cell cancer immunotherapy |
| title | An Ex Vivo 3D Tumor Microenvironment-Mimicry Culture to Study TAM Modulation of Cancer Immunotherapy |
| title_full | An Ex Vivo 3D Tumor Microenvironment-Mimicry Culture to Study TAM Modulation of Cancer Immunotherapy |
| title_fullStr | An Ex Vivo 3D Tumor Microenvironment-Mimicry Culture to Study TAM Modulation of Cancer Immunotherapy |
| title_full_unstemmed | An Ex Vivo 3D Tumor Microenvironment-Mimicry Culture to Study TAM Modulation of Cancer Immunotherapy |
| title_short | An Ex Vivo 3D Tumor Microenvironment-Mimicry Culture to Study TAM Modulation of Cancer Immunotherapy |
| title_sort | ex vivo 3d tumor microenvironment mimicry culture to study tam modulation of cancer immunotherapy |
| topic | tumor-associated macrophage (TAM) tumor microenvironment (TME) ex vivo 3D TME-mimicry culture chimeric antigen receptor (CAR) CAR-engineered T (CAR-T) cell cancer immunotherapy |
| url | https://www.mdpi.com/2073-4409/11/9/1583 |
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