Bartneck, Joschka and Hartmann, Ann-Kathrin and Stein, Lara and Arnold-Schild, Danielle and Klein, Matthias and Stassen, Michael and Marini, Federico and Pielenhofer, Jonas and Meiser, Sophie Luise and Langguth, Peter and Mack, Matthias and Muth, Sabine and Probst, Hans-Christian and Schild, Hansjorg and Radsak, Markus Philipp (2023) Tumor-infiltrating CCR2+ inflammatory monocytes counteract specific immunotherapy. FRONTIERS IN IMMUNOLOGY, 14: 1267866. ISSN 1664-3224,
Full text not available from this repository. (Request a copy)Abstract
Tumor development and progression is shaped by the tumor microenvironment (TME), a heterogeneous assembly of infiltrating and resident host cells, their secreted mediators and intercellular matrix. In this context, tumors are infiltrated by various immune cells with either pro-tumoral or anti-tumoral functions. Recently, we published our non-invasive immunization platform DIVA suitable as a therapeutic vaccination method, further optimized by repeated application (DIVA(2)). In our present work, we revealed the therapeutic effect of DIVA(2) in an MC38 tumor model and specifically focused on the mechanisms induced in the TME after immunization. DIVA(2) resulted in transient tumor control followed by an immune evasion phase within three weeks after the initial tumor inoculation. High-dimensional flow cytometry analysis and single-cell mRNA-sequencing of tumor-infiltrating leukocytes revealed cytotoxic CD8(+) T cells as key players in the immune control phase. In the immune evasion phase, inflammatory CCR2(+) PDL-1(+) monocytes with immunosuppressive properties were recruited into the tumor leading to suppression of DIVA(2)-induced tumor-reactive T cells. Depletion of CCR2(+) cells with specific antibodies resulted in prolonged survival revealing CCR2(+) monocytes as important for tumor immune escape in the TME. In summary, the present work provides a platform for generating a strong antigen-specific primary and memory T cell immune response using the optimized transcutaneous immunization method DIVA(2). This enables protection against tumors by therapeutic immune control of solid tumors and highlights the immunosuppressive influence of tumor infiltrating CCR2(+) monocytes that need to be inactivated in addition for successful cancer immunotherapy.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INTERFERON-GAMMA; IFN-GAMMA; SUPPRESSOR-CELLS; T-CELLS; TRANSCUTANEOUS IMMUNIZATION; CUTTING EDGE; MACROPHAGES; CANCER; CCL2; LYMPHOCYTES; cancer immunotherapy; transcutaneous immunization; tumor micro environment (TME); immune evasion; CCR2 monocytes plus |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Nephrologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 23 Mar 2024 09:00 |
| Last Modified: | 23 Mar 2024 09:00 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60374 |
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