{"id":16014,"date":"2026-05-14T10:52:54","date_gmt":"2026-05-14T14:52:54","guid":{"rendered":"https:\/\/www.med.unc.edu\/cellbiophysio\/?p=16014"},"modified":"2026-05-14T11:05:58","modified_gmt":"2026-05-14T15:05:58","slug":"rewiring-t-cell-signals-in-cancer","status":"publish","type":"post","link":"https:\/\/www.med.unc.edu\/cellbiophysio\/rewiring-t-cell-signals-in-cancer\/","title":{"rendered":"Rewiring T Cell Signals in Cancer"},"content":{"rendered":"

Researchers are developing programmable immune strategies that allow T cells to resist exhaustion and sustain anti\u2011tumor responses.<\/em><\/p>\n

\n

Tumors survive in part by sending \u201cdon\u2019t attack me\u201d signals to T cells. Many current immunotherapies rely on antibody drugs to block these signals, but these treatments don\u2019t work for all patients and can lose effectiveness over time. Kay Chung, an assistant professor in the Department of Cell Biology and Physiology and a member of the UNC Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill, is working to change that.<\/p>\n

\"Kay
Kay Chung recently received a Chan Zuckerberg Biohub Synthetic Biology Award to rewire T cell signaling in cancer.<\/figcaption><\/figure>\n

\u201cWe\u2019re moving beyond simply blocking inhibitory signals,\u201d said Chung. \u201cOur goal is to rewire how T cells interpret those signals\u2014so what normally suppresses them instead activates them.\u201d<\/p>\n

She partnered with Xin Zhou at the Dana-Farber Cancer Institute, her former graduate school colleague with a shared vision of integrating synthetic biology and immunology to create next-generation cell therapies. The two recently received a Chan Zuckerberg Biohub grant to rewire T cell signals, enabling T cells to reinterpret tumor-derived cues and sustain anti-tumor activity. This approach represents a paradigm shift in the field from blocking immune signals with antibodies or drugs to programming how immune cells interpret them.<\/p>\n

Chung\u2019s recent work<\/a> defined the regulatory circuitry that governs T cell state transitions, identifying key transcription factors that drive activation and exhaustion (1). Building on this foundation, she is developing next-generation synthetic platforms to reprogram how T cells interpret signals, integrating transcription factor engineering with programmable intracellular logic circuits.<\/p>\n

Chung and Zhou\u2019s newly funded project through the Chan Zuckerberg Biohub combines Chung\u2019s T cell programming framework with Zhou\u2019s protein engineering to build programmable intracellular signaling systems. Using synthetic protein binders<\/a> developed by Zhou to precisely control intracellular signaling (2), the team plans to engineer T cells that can convert suppressive signals from the tumor microenvironment into activation cues, effectively flipping the signal.<\/p>\n

\"An
Chung\u2019s lab develops synthetic transcription factor and signaling circuit platforms to program T cell behavior.<\/figcaption><\/figure>\n

“When a tumor tries to turn T cells off, we want that signal to do the opposite\u2014to wake them up,\u201d Chung said.<\/strong><\/span><\/p><\/blockquote>\n

Chung and Zhou are also developing a complementary strategy: a drug-controllable system that temporarily disables inhibitory receptors on T cells. Some inhibitory receptors are essential for T cell activity and survival, so completely knocking out those receptors could have negative consequences. \u201cThink of it as a molecular remote control,\u201d Chung said. \u201cWe can tune T cell responses dynamically rather than locking them into a single state.\u201d<\/p>\n

Together, these approaches are designed to create a new class of immunotherapies with greater precision, adaptability, and durability than current treatments. If successful, this work will be a step toward a future in which immune responses can be precisely designed to meet the demands of complex diseases like cancer.<\/p>\n

 <\/p>\n

References<\/strong><\/p>\n

    \n
  1. Chung, H.K., Liu, C., Battu, A., et al<\/em>. Atlas-guided discovery of transcription factors for T cell programing<\/a>. Nature<\/em> 651<\/strong>, 1077-1087 (2026).<\/li>\n
  2. Ma, Zhixing, Hellweg, L., Elledge, S.K., et al<\/em>. Synthetic signaling platform uncovers and rewires cellular responses to PD-1 perturbation<\/a>. bioRxiv<\/em> (2025).<\/li>\n<\/ol>\n

     <\/p>\n

    \n

    Written by Tiffany Garbutt, PhD<\/em><\/p>\n

    For more on the Chan Zuckerberg Biohub Synthetic Biology Award, read the Biohub press release here: https:\/\/biohub.org\/blog\/immune-cell-engineers\/<\/a><\/em><\/p>\n","protected":false},"excerpt":{"rendered":"

    Researchers are developing programmable immune strategies that allow T cells to resist exhaustion and sustain anti\u2011tumor responses. Tumors survive in part by sending \u201cdon\u2019t attack me\u201d signals to T cells. Many current immunotherapies rely on antibody drugs to block these signals, but these treatments don\u2019t work for all patients and can lose effectiveness over time. … Read more<\/a><\/p>\n","protected":false},"author":77299,"featured_media":16042,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"layout":"","cellInformation":"","apiCallInformation":"","footnotes":"","_links_to":"","_links_to_target":""},"categories":[52,2],"tags":[],"featured-item":[],"class_list":["post-16014","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-featured-news","category-news","odd"],"acf":[],"yoast_head":"\nRewiring T Cell Signals in Cancer - Department of Cell Biology and Physiology<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.med.unc.edu\/cellbiophysio\/rewiring-t-cell-signals-in-cancer\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Rewiring T Cell Signals in Cancer - Department of Cell Biology and Physiology\" \/>\n<meta property=\"og:description\" content=\"Researchers are developing programmable immune strategies that allow T cells to resist exhaustion and sustain anti\u2011tumor responses. 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