iRGD synergizes with PD-1 knockout immunotherapy by enhancing lymphocyte infiltration in gastric cancer
| Autor: | Hong Chen, Jia Wei, Naiqing Ding, Lianru Zhang, Shiyao Du, Ju Yang, Zhengyun Zou, Shu Su, Fangjun Chen, Hanqing Qian, Huizi Sha, Baorui Liu, Shujuan Zhou, Fanyan Meng |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine medicine.medical_treatment Lymphocyte Programmed Cell Death 1 Receptor General Physics and Astronomy 02 engineering and technology Polyethylene Glycols Cell therapy Gene Knockout Techniques chemistry.chemical_compound Subcutaneous Tissue Lymphocytes Phosphorylation lcsh:Science Peritoneal Neoplasms Mice Inbred BALB C Multidisciplinary Chemistry Cadherins 021001 nanoscience & nanotechnology Endothelial stem cell medicine.anatomical_structure Immunotherapy 0210 nano-technology Oligopeptides Infiltration (medical) Science Mice Nude Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Immune system Antigens CD Stomach Neoplasms Cell Line Tumor Spheroids Cellular Human Umbilical Vein Endothelial Cells medicine Animals Humans Phosphotyrosine Phosphatidylethanolamines Tyrosine phosphorylation General Chemistry medicine.disease 030104 developmental biology Cancer research lcsh:Q |
| Zdroj: | Nature Communications, Vol 10, Iss 1, Pp 1-9 (2019) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | Poor infiltration of activated lymphocytes into tumors represents a fundamental factor limiting the therapeutic effect of adoptive cell immunotherapy. A tumor-penetrating peptide, iRGD, has been widely used to deliver drugs into tumor tissues. In this study, we demonstrate for the first time that iRGD could also facilitate the infiltration of lymphocytes in both 3D tumor spheroids and several xenograft mouse models. In addition, combining iRGD modification with PD-1 knockout lymphocytes reveals a superior anti-tumor efficiency. Mechanistic studies demonstrate that the binding of iRGD to neuropilin-1 results in tyrosine phosphorylation of the endothelial barrier regulator VE-cadherin, which plays a role in the opening of endothelial cell contacts and the promotion of transendothelial lymphocyte migration. In summary, these results demonstrate that iRGD modification could promote tumor-specific lymphocyte infiltration, and thereby overcome the bottleneck associated with adoptive immune cell therapy in solid tumors. The therapeutic efficacy of adoptive T cell transfer is limited by their ability to infiltrate solid tumours. Here, the authors show that loading the tumor penetrating cyclic peptide iRGD on the cell surface of T cells enhances their ability to penetrate the tumour, resulting in enhanced efficacy in a mouse model of gastric cancer. |
| Databáze: | OpenAIRE |
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