Identification of Immune Cell Infiltration in Murine Pheochromocytoma during Combined Mannan-BAM, TLR Ligand, and Anti-CD40 Antibody-Based Immunotherapy
| Autor: | Veronika Caisova, Rogelio Medina, Jindrich Chmelar, Claudia Palena, Boqun Zhu, Zhengping Zhuang, Ondrej Uher, Thanh-Truc Huynh, Karel Pacak, Lucas A. Horn, Jan Zenka, Katerina Vanova, Herui Wang |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research T cell medicine.medical_treatment immune memory Article Metastasis Pheochromocytoma 03 medical and health sciences 0302 clinical medicine Immune system Medicine RC254-282 Toll-like receptor biology business.industry Neoplasms. Tumors. Oncology. Including cancer and carcinogens Immunotherapy medicine.disease Primary tumor pheochromocytoma intratumoral immunotherapy 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Cancer research biology.protein bilateral tumor model toll-like receptor Antibody business |
| Zdroj: | Cancers, Vol 13, Iss 3942, p 3942 (2021) Cancers Volume 13 Issue 16 |
| ISSN: | 2072-6694 |
| Popis: | Simple Summary Multiple types of primary tumors and metastases that present with very little if any immune cell infiltration (so-called immunologically “cold” tumors) do not respond to current immunotherapies. In this study, we show that recently developed intratumoral application-based immunotherapy using mannan-BAM, TLR ligands, and anti-CD40 antibody (MBTA therapy) efficiently suppresses tumor growth in a murine bilateral pheochromocytoma model. Moreover, MBTA therapy increases the recruitment of innate immune cells followed by adaptive immune cells not only to primary (injected) tumors but also distal (non-injected) tumors. We also demonstrated that after successful MBTA therapy of subcutaneous pheochromocytoma, long-term immunological memory is driven by CD4+ T cells. Taken together, this study helps to better understand the systemic effect of MBTA therapy and its use for tumor and metastasis reduction or even elimination. Abstract Immunotherapy has become an essential component in cancer treatment. However, the majority of solid metastatic cancers, such as pheochromocytoma, are resistant to this approach. Therefore, understanding immune cell composition in primary and distant metastatic tumors is important for therapeutic intervention and diagnostics. Combined mannan-BAM, TLR ligand, and anti-CD40 antibody-based intratumoral immunotherapy (MBTA therapy) previously resulted in the complete eradication of murine subcutaneous pheochromocytoma and demonstrated a systemic antitumor immune response in a metastatic model. Here, we further evaluated this systemic effect using a bilateral pheochromocytoma model, performing MBTA therapy through injection into the primary tumor and using distant (non-injected) tumors to monitor size changes and detailed immune cell infiltration. MBTA therapy suppressed the growth of not only injected but also distal tumors and prolonged MBTA-treated mice survival. Our flow cytometry analysis showed that MBTA therapy led to increased recruitment of innate and adaptive immune cells in both tumors and the spleen. Moreover, adoptive CD4+ T cell transfer from successfully MBTA-treated mice (i.e., subcutaneous pheochromocytoma) demonstrates the importance of these cells in long-term immunological memory. In summary, this study unravels further details on the systemic effect of MBTA therapy and its use for tumor and metastasis reduction or even elimination. |
| Databáze: | OpenAIRE |
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