{"id":951735,"date":"2026-10-30T09:42:18","date_gmt":"2026-10-30T09:42:18","guid":{"rendered":"https:\/\/www.newsbeep.com\/ca\/951735\/"},"modified":"2026-10-30T09:42:18","modified_gmt":"2026-10-30T09:42:18","slug":"perforin-michigan-researchers-find-immune-protein-kills-cancer-by-overloading-it-with-iron","status":"publish","type":"post","link":"https:\/\/www.newsbeep.com\/ca\/951735\/","title":{"rendered":"Perforin: Michigan researchers find immune protein kills cancer by overloading it with iron"},"content":{"rendered":"

\"Perforin<\/a>Perforin increases endosomal-mitochondrial contact sites in tumor cells. Left has no perforin; right is with perforin<\/p>\n

Credit University of Michigan Rogel Cancer Center
\n Research from the University of Michigan Health Rogel Cancer Centre overturns decades of accepted immunological science by showing that perforin, a protein produced by T cells and natural killer (NK) cells, can destroy tumour cells on its own, without requiring digestive enzymes known as granzymes<\/p>\n

The study, published in Cell,<\/a> reveals that perforin alone triggers ferroptosis, an iron-dependent form of programmed cell death, identifying a previously unknown pathway for anti-tumour immunity.<\/p>\n

The ferroptosis mechanism and cellular disruption<\/p>\n

For decades, textbook immunology posited that perforin merely functioned as a pore-forming delivery tool (\u201cthe weapon\u201d) designed to inject granzymes (\u201cthe ammunition\u201d) into cancer cells to initiate apoptosis.<\/p>\n

The U-M research team, led by Dr Weiping Zou, Dr Ilona Kryczek, and Harvard\u2019s Dr Judy Lieberman, proved that perforin initiates an independent lethal cascade:<\/p>\n

Membrane and iron uptake disruption:<\/p>\n

In addition to punching holes in the plasma membrane, perforin alters cellular iron regulation, causing an abnormal influx and accumulation of iron inside the host cell and its mitochondria.<\/p>\n

Mitochondrial lipid peroxidation:<\/p>\n

Excess intra-mitochondrial iron triggers rapid oxidation of lipids (fats), causing catastrophic organelle dysfunction.<\/p>\n

Ferroptotic cascade:<\/p>\n

The accumulation of toxic lipid peroxides drives the cell into ferroptosis, an iron-dependent form of cell death distinct from traditional apoptosis or pyroptosis.<\/p>\n

Experimental validation and clinical observations<\/p>\n

The research team established perforin\u2019s independent cytotoxicity across three distinct experimental frameworks:<\/p>\n

In vitro genetic manipulations:<\/p>\n

Biochemical assays confirmed that tumour cells lacking granzyme activity still underwent rapid cell death when exposed to isolated perforin via ferroptosis.<\/p>\n

In vivo animal models:<\/p>\n

Mouse models on controlled iron diets showed significant reductions in tumour growth rates directly correlated with T-cell perforin expression.<\/p>\n

Human patient cohorts:<\/p>\n

Analysis of clinical data revealed that cancer patients with higher perforin levels had better overall survival and significantly stronger responses to immune checkpoint blockade therapies.<\/p>\n

Editor’s Recommended Articles<\/p>\n","protected":false},"excerpt":{"rendered":"Perforin increases endosomal-mitochondrial contact sites in tumor cells. Left has no perforin; right is with perforin Credit University…\n","protected":false},"author":2,"featured_media":951736,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[7],"tags":[49,48,3877,33974,7717,66],"class_list":["post-951735","post","type-post","status-publish","format-standard","has-post-thumbnail","category-science","tag-ca","tag-canada","tag-cancer-research","tag-genetic-research","tag-immune-system","tag-science"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/posts\/951735","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/comments?post=951735"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/posts\/951735\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/media\/951736"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/media?parent=951735"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/categories?post=951735"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/tags?post=951735"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}