{"id":59669,"date":"2026-03-25T12:38:16","date_gmt":"2026-03-25T11:38:16","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/03\/25\/human-macrophage-phagocytosis-of-lung-cancer-cells-induced-by-cd47-blockade-is-augmented-after-knockdown-of-phagocytosis-checkpoints-mediated-by-sirna-loaded-lipid-nanoparticleskristian-w-ant\/"},"modified":"2026-03-25T12:38:16","modified_gmt":"2026-03-25T11:38:16","slug":"human-macrophage-phagocytosis-of-lung-cancer-cells-induced-by-cd47-blockade-is-augmented-after-knockdown-of-phagocytosis-checkpoints-mediated-by-sirna-loaded-lipid-nanoparticleskristian-w-ant","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/03\/25\/human-macrophage-phagocytosis-of-lung-cancer-cells-induced-by-cd47-blockade-is-augmented-after-knockdown-of-phagocytosis-checkpoints-mediated-by-sirna-loaded-lipid-nanoparticleskristian-w-ant\/","title":{"rendered":"Human macrophage phagocytosis of lung cancer cells induced by CD47 blockade is augmented after knockdown of phagocytosis checkpoints mediated by siRNA-loaded lipid nanoparticles\u200bKristian W Antonsen on 25 de March de 2026 at 10:00"},"content":{"rendered":"
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J Leukoc Biol<\/b>. 2026 Mar 25:qiag043. doi: 10.1093\/jleuko\/qiag043. Online ahead of print.<\/p>\n

ABSTRACT<\/b><\/p>\n

Macrophages can phagocytose tumor cells. However, tumor cells may avoid phagocytosis by activating macrophage-expressed phagocytosis checkpoints such as SIRP\u03b1, LILRB1, or Siglec-10. Here, we investigated if LNPs loaded with siRNA (siRNA-LNPs) specifically neutralizing these checkpoints may be used as a counter-regulatory approach to augment cancer cell phagocytosis in human macrophages. The NanoAssemblr Ignite platform was used to prepare siRNA-LNPs targeting genes of interest. Human monocyte-derived macrophages were generated in vitro from healthy anonymous blood donors and treated with one or more siRNA-LNPs under various conditions. Following treatments, abundance of mRNA was analyzed by RT-qPCR, while membrane protein and soluble protein was measured by flow cytometry and ELISA, respectively. Phagocytosis was assessed by flow cytometry and fluorescence microscopy. Target mRNAs were efficiently downregulated by siRNA-LNPs in a dose-dependent manner. Combination treatment targeting all three genes of interest was similar in knockdown effectiveness to single treatment for each target. A single dose resulted in significant downregulation of mRNA and protein for up to 7 days and did not reduce macrophage viability. Repeated dosing further reduced target abundance. Importantly, we observed a synergy between LILRB1-siRNA-LNPs and CD47 blockade that increased macrophage phagocytosis of NCI-H196 lung cancer cells. In conclusion, transfection with siRNA-LNPs resulted in an efficient simultaneous downregulation of phagocytosis checkpoints in human macrophages and augmented macrophage phagocytosis of tumor cells in response to CD47 blockade in vitro. Using siRNA-LNPs in cancer therapy may be a promising potential approach to augment phagocytosis and the innate immune response against tumor growth.<\/p>\n

PMID:41876763<\/a> | DOI:10.1093\/jleuko\/qiag043<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"

J Leukoc Biol. 2026 Mar 25:qiag043. doi: 10.1093\/jleuko\/qiag043. Online ahead of print. ABSTRACT Macrophages can phagocytose tumor cells. However, tumor cells may avoid phagocytosis by activating macrophage-expressed phagocytosis checkpoints such as SIRP\u03b1, LILRB1, or Siglec-10. Here, we investigated if LNPs loaded with siRNA (siRNA-LNPs) specifically neutralizing these checkpoints may be used as a counter-regulatory approach … Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[86,42],"tags":[],"class_list":["post-59669","post","type-post","status-publish","format-standard","hentry","category-journal-of-leukocyte-biology","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/59669","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=59669"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/59669\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=59669"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=59669"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=59669"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}