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'PSGL-1 attenuates early TCR signaling to suppress CD8+T cell progenitor differentiation and elicit terminal CD8+T cell exhaustion'ÀÔ´Ï´Ù.
À§ ³í¹®Àº exhaustion checkpoint regulator¶ó°í ¾Ë·ÁÁø PSGL-1(P-selectin glycoprotein-1)ÀÇ ÀÛ¿ë±âÀü¿¡ ´ëÇÏ¿© ¿¬±¸ÇÑ ³í¹®ÀÔ´Ï´Ù.
¿¬±¸ÁøÀº effector »óÅÂ¿Í exhaustion »óÅ ¸ðµÎ¿¡¼ PSGL-1ÀÌ KOµÇ¾úÀ» ½Ã low affinity TCR signal¿¡ ¹Î°¨Çϸç, in vivo »óÀ¸·Î exhaustion »óŸ¦ À¯µµÇÏ´Â tumorȯ°æ¿¡ Àû¿ëÇßÀ» ½Ã¿¡µµ exhaustion state·ÎÀÇ ºÐȸ¦ ¸·À» ¼ö ÀÖÀ½À» TCF-1°úTOXÀÇ ¹ßÇö Á¤µµ¸¦ ÅëÇÏ¿© È®ÀÎÇÏ¿´½À´Ï´Ù.
ÀÌ·¯ÇÑ °á°ú°¡ °¡´ÉÇÏ°Ô ÇÔÀº, PSGL-1ÀÌ TCR complex °áÂûÇϴµ¥ Á÷Á¢ÀûÀ¸·Î ¿ªÇÒ ÇÔÀ» È®ÀÎÇÏ¿´°í,
´õºÒ¾î ZAP70 inhibitorÀÎ STS-1ÀÇ ¹ßÇöÀ» ¸·À½À¸·Î½á TCR signaling¿¡ ¹Î°¨ÇÒ ¼ö ÀÖÀ½À» ¼³¸íÇÏ¿´½À´Ï´Ù.
´õºÒ¾î, À̸¦ ÈÞ¸Õ¿¡ Àû¿ëÇÏ¿© ¾à¸®ÇÐÀûÀ¸·Î PSGL-1À» Â÷´ÜÇÏ¿´À» ½Ã exhaustion state·ÎÀÇ °í°¥À» ¾ïÁ¦ÇÏ¿© tumor growth¸¦ Á¦¾îÇÏ´Â °ÍÀ¸·Î º¸¾Æ, ICB¿¡ ³»¼ºÀÌ ÀÖ´Â tumor¸ðµ¨¿¡¼ immuno-therapeutic targetÀÌ µÉ °¡´É¼ºÀ» ½Ã»çÇÏ¸ç ¸¶¹«¸® ÇÏ¿´½À´Ï´Ù.
ÇØ´ç ³í¹®À» ¼±Á¤ÇÏ°Ô µÈ ÀÌÀ¯´Â Àúµµ tumor¿¡¼ exhaustion state¸¦ ÃøÁ¤ÇÏ´Â ¹ý°ú, TCR signaling ºÎºÐ¿¡¼ ¿¬±¸¸¦ Ç®¾î³ª°¡´Â ºÎºÐ¿¡ ´ëÇؼ °øºÎÇغ¸°íÀÚ ¼±Á¤ÇÏ¿´½À´Ï´Ù.