{"id":490636,"date":"2026-01-05T16:17:00","date_gmt":"2026-01-05T08:17:00","guid":{"rendered":"https:\/\/www.um.edu.mo\/news-and-press-releases\/campus-news\/detail\/62917-2\/"},"modified":"2026-01-05T16:34:30","modified_gmt":"2026-01-05T08:34:30","slug":"62917","status":"publish","type":"post","link":"https:\/\/www.um.edu.mo\/pt-pt\/news-and-press-releases\/campus-news\/detail\/62917\/","title":{"rendered":"UM unravels \u2018double lock\u2019 mechanism of immune checkpoints, offering insight for optimising anti-cancer immunotherapies"},"content":{"rendered":"\n                        \n                        <p><a name=\"_Hlk213334818\">A research team led by Tang Zhenghai, assistant professor in the Faculty\nof Health Sciences at the University of Macau (UM), has engineered a bispecific\nantibody capable of simultaneously blocking both the SIRP\u03b1\u2013CD18 and SIRP\u03b1\u2013CD47\ninteractions, markedly enhancing macrophage phagocytosis and significantly\ninhibiting tumour growth. This newly identified immune mechanism could improve\ncancer treatment and provides a promising target for developing more precise\nand less toxic immunotherapies. The findings have been published in the\nprestigious international journal <i>Science\nImmunology<\/i>.<\/a><\/p>\n\n<p>While antibodies that block the inhibitory\ncheckpoints PD-1 or CTLA-4 have achieved remarkable success in recent years,\nmany patients still experience limited or short-lived responses. These\nchallenges have prompted researchers to explore other immune cells,\nparticularly macrophages, which play a key role in tumour immunity. SIRP\u03b1 is a\nclassical inhibitory receptor on macrophages. When bound to CD47, which is\nfrequently overexpressed on tumour cells, SIRP\u03b1 sends inhibitory signals that\nblock macrophage-mediated phagocytosis and anti-tumour immunity.\nAlthough therapies targeting the SIRP\u03b1\u2013CD47 axis can enhance anti-tumour\nimmunity, clinical results have been inconsistent, and some patients have experienced\nside effects, suggesting that other suppressive mechanisms may be involved.<\/p>\n\n<p>The UM research team has identified a\npathway that helps explain this phenomenon. Their study showed that even when\nthe SIRP\u03b1\u2013CD47 interaction was disrupted, macrophages still displayed partial\ninhibition. They found that SIRP\u03b1 directly cis interacts\nwith CD18 on the cell surface of macrophages,\nrestraining CD18 activation and macrophage phagocytosis. This\nSIRP\u03b1-CD18 interaction\noccurs on the same cell surface and works together with the known pathway to\nsuppress the immune response. To translate these findings into potential\ntherapy, the team engineered a bispecific antibody capable of simultaneously\nblocking both the SIRP\u03b1\u2013CD18 and SIRP\u03b1\u2013CD47 interactions. This antibody\nmarkedly enhanced macrophage phagocytosis and significantly inhibited tumour\ngrowth in mouse models, demonstrating stronger anti-tumour effects than\nantibodies blocking either pathway alone.<\/p>\n\n<p>Tang notes that immune checkpoints are more complex than initially\nexpected. He emphasises that deeper\nknowledge of their molecular mechanisms is essential for designing safer and\nmore effective cancer therapies. The team\u2019s study reveals a dual-inhibitory\nmode of immune regulation and offers valuable insight for optimising\nnext-generation immunotherapies.<\/p>\n\n\n\n<p>The study is co-authored by Tang and Andr\u00e9 Veillette, professor at the\nMontreal Clinical Research Institute, with Tang as the first author, and Tang\nand Veillette as corresponding authors. The research was supported by the\nScience and Technology Development Fund of the Macao SAR (File No: 0090\/2024\/RIB2) and UM (File No:\nSRG2024-00027-FHS and UMDF-TISF\/2025\/002\/FHS). The full version of the study is\navailable at: <a href=\"https:\/\/www.science.org\/doi\/10.1126\/sciimmunol.adv5085\">https:\/\/www.science.org\/doi\/10.1126\/sciimmunol.adv5085<\/a>.<\/p>\n\n<table style=\"width: 44.7597%;height: 201px\"> <tbody> <tr style=\"height: 21px\"> <td style=\"height: 21px;width: 100.095%\" colspan=\"2\">Source: Faculty of Health Sciences<\/td> <\/tr> <tr style=\"height: 21px\"> <td style=\"height: 21px;width: 56.3278%;min-width: 120px\"> <\/td> <td style=\"height: 21px;width: 43.7669%\"> <\/td> <\/tr> <tr style=\"height: 21px\"> <td style=\"height: 21px;width: 100.095%\" colspan=\"2\">Media Contact Information:<\/td> <\/tr> <tr style=\"height: 21px\"> <td style=\"height: 12px;width: 100.095%\" colspan=\"2\">Communications Office, University of Macau<\/td> <\/tr> <tr style=\"height: 21px\"> <td style=\"height: 21px;width: 56.3278%;min-width: 120px\"> <\/td> <td style=\"height: 21px;width: 43.7669%\"> <\/td> <\/tr> <tr style=\"height: 21px\"> <td style=\"height: 21px;width: 56.3278%;min-width: 120px\">Albee Lei<\/td> <td style=\"height: 21px;width: 43.7669%\">Tel: (853) 8822 8004<\/td> <\/tr> <tr style=\"height: 21px\"> <td style=\"height: 21px;width: 56.3278%;min-width: 120px\">Bell Leong<\/td> <td style=\"height: 21px;width: 43.7669%\">Tel: (853) 8822 8009<\/td> <\/tr> <tr style=\"height: 21px\"> <td style=\"height: 21px;width: 56.3278%;min-width: 120px\">Email:<\/td> <td style=\"height: 21px;width: 43.7669%\"><a href=\"mailto:prs.media@um.edu.mo\">prs.media@um.edu.mo<\/a><\/td>\n<\/tr>\n<tr style=\"height: 21px\">\n<td style=\"height: 21px;width: 56.3278%;min-width: 120px\"> <\/td> <td style=\"height: 21px;width: 43.7669%\"> <\/td> <\/tr> <tr style=\"height: 21px\"> <td style=\"height: 21px;width: 56.3278%;min-width: 120px\"><\/td><td style=\"height: 21px;width: 43.7669%\"><\/td><\/tr>\n<\/tbody>\n<\/table>\n                        \n                        ","protected":false},"excerpt":{"rendered":"<p>A research team led by Tang Zhenghai, assistant professor in the Faculty of Health Sciences at the University of Macau (UM), has engineered a bispecific antibody capable of simultaneously blocking&#8230;<\/p>\n","protected":false},"author":1,"featured_media":490666,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[61],"tags":[],"class_list":["post-490636","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-campus-news"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v24.5 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>UM unravels \u2018double lock\u2019 mechanism of immune checkpoints, offering insight for optimising anti-cancer immunotherapies | Universidade de Macau<\/title>\n<meta name=\"description\" content=\"Universidade de Macau: Uma universidade abrangente p\u00fablica de n\u00edvel internacional fundada em 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