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À̹ø ÁÖ ¹ßÇ¥ ³í¹®Àº 2023³â 7¿ù¿¡ Science immunology¿¡ ÃâÆÇµÈ 'Restoring Tumor Immunogenicity with Dendritic Cell Reprogramming'ÀÔ´Ï´Ù.
Cancer cellÀº immune checkpoint inhibitor moleculeÀÇ ¹ßÇö, tumor neoantigen µîÀÇ editing, ±×¸®°í antigen presentationÀÇ ÇÏÇâ Á¶Àý µî ´Ù¾çÇÑ ¸ÞÄ¿´ÏÁòÀ» ÅëÇØ immune evasionÀ» ÀÏÀ¸Å°´Â °ÍÀ¸·Î ¾Ë·ÁÁ® ÀÖ½À´Ï´Ù.
ÀÌ·¯ÇÑ º¯È´Â antigen processing & presentation µî¿¡ °ü¿©ÇÏ´Â geneµéÀÇ transcriptional & epigenetic down-regulation¿¡ ÀÇÇؼ Á¶ÀýµÈ´Ù°í ¾Ë·ÁÁ® ÀÖ½À´Ï´Ù.
º» ¿¬±¸ÆÀÀº ¿ì¼± type 1 conventional dendritic cell (cDC1)ÀÇ transcription factor¸¦ Æ÷ÇÔÇÏ´Â lentiviral vectorÀ» »ç¿ëÇÏ¿© ´Ù¾çÇÑ À¯·¡ÀÇ tumor cell lineµéÀ» professional antigen presenting cells (tumor-APCs)·Î reprogramming ÇÏ¿´½À´Ï´Ù.
reprogrammed tumor-APCsÀÇ transcriptional & epigenetic program À» ºñ±³ÇÏ¿´À¸¸ç, antigen presentation complex, costimulatory moleculeÀÇ expression ¶ÇÇÑ È®ÀÎÇÏ¿´½À´Ï´Ù.
¶ÇÇÑ tumor-APC°¡ exogenousÇÑ proteinÀ̳ª dead cellsÀ» engulfÇÏ¿© naive CD8 T cell¿¡°Ô Á¦½ÃÇÏ´Â cross-presentationÀ» ¼öÇàÇÒ ¼ö ÀÖÀ½À» ¹àÇû½À´Ï´Ù.
ÀÌÈÄ Human primary tumor cellÀ» »ç¿ëÇÏ¿© µ¿ÀÏÇÑ lentiviral vector systemÀ¸·Î tumor-APCs Çü¼º ¹× antigen presentation capacity¸¦ È®ÀÎÇÏ¿´½À´Ï´Ù.
ÃÖÁ¾ÀûÀ¸·Î in vivo¿¡¼ tumor-APCs¸¦ intratumoral injectionÇÏ¿© tumor growth¸¦ ´ÊÃß°í »ýÁ¸À²À» Áõ°¡½ÃÅ°´Â °ÍÀ» °üÂûÇÏ¿´½À´Ï´Ù.
Áï, À§ ³í¹®Àº cancer cell¿¡ endogenous tumor antigenÀ» process ¹× presentÇÒ ¼ö ÀÖ´Â ´É·ÂÀ» ºÎ¿©ÇÏ¿© anti tumor immunity¸¦ È®ÀÎÇÏ¿´À¸¸ç »õ·Î¿î immunotherapyÀÇ °¡´É¼ºÀ» È®ÀÎÇÏ¿´½À´Ï´Ù.
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Restoring Tumor Immunogenicity with Dendritic Cell Reprogramming