Autor: |
Siqi Li, Kun Li, Kang Wang, Haoyuan Yu, Xiangyang Wang, Mengchen Shi, Zhixing Liang, Zhou Yang, Yongwei Hu, Yang Li, Wei Liu, Hua Li, Shuqun Cheng, Linsen Ye, Yang Yang |
Jazyk: |
angličtina |
Rok vydání: |
2023 |
Předmět: |
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Zdroj: |
Nature Communications, Vol 14, Iss 1, Pp 1-21 (2023) |
Druh dokumentu: |
article |
ISSN: |
2041-1723 |
DOI: |
10.1038/s41467-023-43462-1 |
Popis: |
Abstract Atezolizumab (anti-PD-L1) combined with bevacizumab (anti-VEGFA) is the first-line immunotherapy for advanced hepatocellular carcinoma (HCC), but the number of patients who benefit from this regimen remains limited. Here, we combine dual PD-L1 and VEGFA blockade (DPVB) with low-dose radiotherapy (LDRT), which rapidly inflames tumors, rendering them vulnerable to immunotherapy. The combinatorial therapy exhibits superior antitumor efficacy mediated by CD8+ T cells in various preclinical HCC models. Treatment efficacy relies upon mobilizing exhausted-like CD8+ T cells (CD8+ Tex) with effector function and cytolytic capacity. Mechanistically, LDRT sensitizes tumors to DPVB by recruiting stem-like CD8+ Tpex, the progenitor exhausted CD8+ T cells, from draining lymph nodes (dLNs) into the tumor via the CXCL10/CXCR3 axis. Together, these results further support the rationale for combining LDRT with atezolizumab and bevacizumab, and its clinical translation. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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