التفاصيل البيبلوغرافية
| العنوان: |
Hyaluronic acid-bilirubin nanomedicine-based combination chemoimmunotherapy. |
| المؤلفون: |
Lee, Yonghyun, Shinn, Jongyoon, Xu, Cheng, Dobson, Hannah E., Neamati, Nouri, Moon, James J. |
| المصدر: |
Nature Communications; 8/8/2023, Vol. 14 Issue 1, p1-14, 14p |
| مصطلحات موضوعية: |
MYELOID-derived suppressor cells, REGULATORY T cells, NANOMEDICINE, PROGRAMMED cell death 1 receptors, MYELOID cells, CELL death, SUPPRESSOR cells, IMMUNE checkpoint proteins |
| مستخلص: |
Despite significant advances in immune checkpoint blockade (ICB), immunosuppression mediated by tumor-associated myeloid cells (TAMCs) poses a major barrier to cancer immunotherapy. In addition, while immunogenic cell death (ICD) provides a viable approach to inducing anti-tumor immune response, it remains unknown how to effectively trigger ICD while addressing immunosuppressive TAMCs. Here, we show that SC144, a gp130 inhibitor that blocks the IL-6/gp130/STAT3 pathway, induces ICD of tumor cells and polarizes macrophages to M1-phenotype in vitro. However, as SC144 also induces killing of CD8+ T-cells, we sought to deliver SC144 selectively to tumor cells and TAMCs. Toward this goal, we have developed hyaluronic acid-bilirubin nanoparticles (HABN) that accumulate in CD44hi tumor cells and TAMCs. Systemic administration of SC144 loaded in HABN (SC144@HABN) induces apoptosis and ICD of tumor cells, increases the ratio of M1-like to M2-like macrophages, and decreases the frequency of myeloid-derived suppressor cells and CD4+ regulatory T-cells, while promoting anti-tumor CD8+ T-cells. Moreover, SC144@HABN combined with anti-PD-L1 ICB efficiently eliminates MC38 tumors and ICB-resistant 4T1 tumors. Overall, our work demonstrates a therapeutic strategy based on coordinated ICD induction and TAMC modulation and highlights the potential of combination chemoimmunotherapy. Immunosuppressive tumour immune microenvironments (TME) limit the success of immune checkpoint blockade (ICD). Here, the authors develop a hyaluronic acid-bilirubin nanoparticle (HABN) capable of inducing immunogenic cell death in tumour cells and altering the TME, resulting in increased sensitivity to ICB (anti-PD-L1) in preclinical models of colorectal cancer and breast cancer. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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