| Autor: |
Edgardo D. Carosella, Lucía Natalia Moro, Ana María Inda, Isabelle Poras, Guadalupe Amín, María Agustina Scarafía, Alejandro La Greca, Santiago Gabriel Miriuka, Marcela Nilda García, Diana Tronik-Le Roux, Alan Miqueas Möbbs, María Belén Palma, Marina Daouya, Sheila Castañeda |
| Rok vydání: |
2021 |
| Předmět: |
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| Popis: |
Cancer immunotherapies based mainly on the blockade of immune-checkpoint (IC) molecules by anti-IC antibodies offer new alternatives for treatment in oncological diseases. However, a considerable proportion of patients remain unresponsive to them. Hence, the development of novel clinical immunotherapeutic approaches and/or targets are crucial. In this context, targeting the immune-checkpoint HLA-G/ILT2/ILT4 has caused great interest since it is abnormally expressed in several malignancies generating a tolerogenic microenvironment. Here, we used CRISPR/Cas9 gene editing to block the HLA-G expression in two tumor cell lines expressing HLA-G, including a renal cell carcinoma (RCC7) and a choriocarcinoma (JEG-3). Different sgRNA/Cas9 plasmids targeting HLA-G exon 1 and 2 were transfected in both cell lines. Downregulation of HLA-G was reached to different degrees, including complete silencing. Most importantly, HLA-G – cells triggered a higher in vitro response of immune cells with respect to HLA-G + wild type cells. Altogether, we demonstrated for the first time the HLA-G downregulation through gene editing. We propose this approach as a first step to develop novel clinical immunotherapeutic approaches in cancer. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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