HLA-G gene editing in tumor cell lines as a novel alternative in cancer immunotherapy

Autor: Alejandro La Greca, Marcela Nilda García, Marina Daouya, Diana Tronik-Le Roux, Sheila Castañeda, Lucía Natalia Moro, Alan Miqueas Möbbs, Ana María Inda, Edgardo D. Carosella, Guadalupe Amín, Santiago Gabriel Miriuka, María Belén Palma, María Agustina Scarafía, Isabelle Poras
Rok vydání: 2021
Předmět:
Zdroj: Scientific Reports
Scientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
ISSN: 2045-2322
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.W 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
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