Macrophage activation by a substituted pyrimido[5,4-b]indole increases anti-cancer activity
| Autor: | Joseph Hardie, Erik M. Rizzo, Michelle E. Farkas, Javier A. Mas-Rosario, Siyoung Ha |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Indoles medicine.medical_treatment Phagocytosis Antineoplastic Agents CD47 Antigen Article Cell Line Small Molecule Libraries 03 medical and health sciences Mice 0302 clinical medicine Immune system medicine Animals 030304 developmental biology Pharmacology 0303 health sciences biology Activator (genetics) Chemistry Macrophages Immunotherapy Macrophage Activation Small molecule Phenotype 3. Good health 030104 developmental biology RAW 264.7 Cells 030220 oncology & carcinogenesis biology.protein TLR4 Cancer research Antibody Adjuvant |
| Zdroj: | Pharmacol Res |
| Popis: | Immunotherapy has become a promising new approach for cancer treatment due to the immune system’s ability to remove tumors in a safe and specific manner. Many tumors express anti-inflammatory factors that deactivate the local immune response or recruit peripheral macrophages into pro-tumor roles. Because of this, effective and specific ways of activating macrophages into anti-tumor phenotypes is highly desirable for immunotherapy purposes. Here, the use of a small molecule TLR agonist as a macrophage activator for anti-cancer therapy is reported. This compound, referred to as PBI1, demonstrated unique activation characteristics and expression patterns compared to treatment with LPS, through activation of TLR4. Furthermore, PBI1 treatment resulted in anti-tumor immune behavior, enhancing macrophage phagocytic efficiency five-fold versus non-treated macrophages. Additive effects were observed via use of a complementary strategy (anti-CD47 antibody), resulting in ∼10-fold enhancement of phagocytosis, suggesting this small molecule approach could be used in conjunction with other therapeutics. |
| Databáze: | OpenAIRE |
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