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An Ex Vivo 3D Tumor Microenvironment-Mimicry Culture to Study TAM Modulation of Cancer Immunotherapy
| Content Provider | MDPI |
|---|---|
| Author | Li, Yan-Ruide Yu, Yanqi Kramer, Adam Hon, Ryan Wilson, Matthew Brown, James Yang, Lili |
| Copyright Year | 2022 |
| 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. |
| Starting Page | 1583 |
| e-ISSN | 20734409 |
| DOI | 10.3390/cells11091583 |
| Journal | Cells |
| Issue Number | 9 |
| Volume Number | 11 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2022-05-08 |
| Access Restriction | Open |
| Subject Keyword | Cells Oncology 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 Checkpoint Inhibitor Blockade Monoamine Oxidase A (mao-a) Blockade |
| Content Type | Text |
| Resource Type | Article |