Targeting PKMYT1 enhances antitumor immune responses in castration-resistant prostate cancer

Targeting PKMYT1 enhances antitumor immune responses in castration-resistant prostate cancer | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Targeting PKMYT1 enhances antitumor immune responses in castration-resistant prostate cancer Bo Han, Lin Gao, Baozhen Wang, Hui Liu, Ping Liu, Long Liu, Jingying Han, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5648993/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Immunotherapy has achieved significant success in treating various cancers, yet its efficacy in castration resistant prostate cancer (CRPC) is minimal, partly due to the lack of intratumoral immune effector cells in CRPC. Understanding the mechanisms of immune evasion and identifying potential therapeutic strategies to activate innate antitumor immunity are crucial for enhancing the response to immunotherapy. Here we demonstrate that PKMYT1, a member of the WEE1 family, is overexpressed in CRPC tissues. Patients with high PKMYT1 expression exhibit low CD8+ T cells infiltration and resistance to immune checkpoint blockade (ICB). Targeting PKMYT1 can suppress CRPC progression, accompanied with increased intratumoral CD8+ T cells. Selective PKMYT1 inhibitor, RP-6306, augments ICB at the presence of CD8+ T cells. PKMYT1 inhibitor alone or in combination with PD-L1 blockade increases infiltration of CD8+ T cell and remarkable tumor suppression in vivo. Mechanically, targeting PKMYT1 activates the cGAS-STING pathway, enhances interferon signaling, and elevates key immune modulators, including CCL5 and CXCL10. These findings highlight a key role of PKMYT1 in CRPC progression and suggest PKMYT1 as a potential therapeutic target in combination with ICB. Health sciences/Urology/Prostate Health sciences/Oncology/Cancer/Urological cancer/Prostate cancer CRPC PKMYT1 STING IFN antitumor immune respo Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryData.pdf Targeting PKMYT1 enhances antitumor immune responses in castration-resistant prostate cancer Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5648993","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":391435970,"identity":"4235c332-780c-4141-98d5-0039cef3a8cb","order_by":0,"name":"Bo 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