Your browser doesn't support javascript.
loading
RNA-based modulation of macrophage-mediated efferocytosis potentiates antitumor immunity in colorectal cancer.
Zhou, Xuefei; Li, Dezhi; Xia, Shenglong; Ma, Xixi; Li, Rong; Mu, Yongli; Liu, Zimo; Zhang, Lu; Zhou, Quan; Zhuo, Wei; Ding, Kefeng; Lin, Aifu; Liu, Wei; Liu, Xiangrui; Zhou, Tianhua.
Afiliación
  • Zhou X; International Institutes of Medicine, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu 322000, China. Electronic address: zhouxf@zju.edu.cn.
  • Li D; Department of Oncology, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu 322000, China.
  • Xia S; Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China; Cancer Center, Zhejiang University, Hangzhou 310058, China.
  • Ma X; Department of Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, China; Center for Medical Research and Innovation in Digestive System Tumors, Ministry of Education, Hangzhou, Zhejiang 310020, China.
  • Li R; Department of Pharmacology, Zhejiang University School of Medicine, Hangzhou 310058, China.
  • Mu Y; Department of Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.
  • Liu Z; Department of Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.
  • Zhang L; Department of Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.
  • Zhou Q; Department of Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.
  • Zhuo W; Department of Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.
  • Ding K; Center for Medical Research and Innovation in Digestive System Tumors, Ministry of Education, Hangzhou, Zhejiang 310020, China.
  • Lin A; College of Life Sciences, Zhejiang University, Hangzhou 310058, China.
  • Liu W; International Institutes of Medicine, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu 322000, China.
  • Liu X; Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China; Cancer Center, Zhejiang University, Hangzhou 310058, China; Department of Pharmacology, Zhejiang University School of Medicine, Hangzhou 310058, China; Innovation Center
  • Zhou T; Cancer Center, Zhejiang University, Hangzhou 310058, China; Department of Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, China; Center for Medical Research and Innovation in Digestive System Tumors, Ministry of Education, Hangzhou, Zhejiang 310020, China. Electronic address:
J Control Release ; 366: 128-141, 2024 Feb.
Article en En | MEDLINE | ID: mdl-38104775
ABSTRACT
Tumor-associated macrophages play pivotal roles in tumor progression and metastasis. Macrophage-mediated clearance of apoptotic cells (efferocytosis) supports inflammation resolution, contributing to immune evasion in colorectal cancers. To reverse this immunosuppressive process, we propose a readily translatable RNA therapy to selectively inhibit macrophage-mediated efferocytosis in tumor microenvironment. A clinically approved lipid nanoparticle platform (LNP) is employed to encapsulate siRNA for the phagocytic receptor MerTK (siMerTK), enabling selective MerTK inhibition in the diseased organ. Decreased MerTK expression in tumor-associated macrophages results in apoptotic cell accumulation and immune activation in tumor microenvironment, leading to suppressed tumor growth and better survival in both liver and peritoneal metastasis models of colorectal cancers. siMerTK delivery combined with PD-1 blockade further produces enhanced antimetastatic efficacy with reactivated intratumoral immune milieu. Collectively, LNP-based siMerTK delivery combined with immune checkpoint therapy may present a feasible modality for metastatic colorectal cancer therapy.
Asunto(s)
Palabras clave

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias del Colon / Eferocitosis Límite: Humans Idioma: En Revista: J Control Release Asunto de la revista: FARMACOLOGIA Año: 2024 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias del Colon / Eferocitosis Límite: Humans Idioma: En Revista: J Control Release Asunto de la revista: FARMACOLOGIA Año: 2024 Tipo del documento: Article
...