Superparamagnetic iron oxide nanoparticles reprogram the tumor microenvironment and reduce lung cancer regrowth after Crizotinib treatment

• Verfasst von: Horvat, Natalie [VerfasserIn]
• Verfasst von: Chocarro, Sara [VerfasserIn]
• Verfasst von: Marques, Oriana [VerfasserIn]
• Verfasst von: Bauer, Tobias A. [VerfasserIn]
• Verfasst von: Qiu, Ruiyue [VerfasserIn]
• Verfasst von: Díaz-Jiménez, Alberto [VerfasserIn]
• Verfasst von: Helm, Barbara [VerfasserIn]
• Verfasst von: Chen, Yuanyuan [VerfasserIn]
• Verfasst von: Sawall, Stefan [VerfasserIn]
• Verfasst von: Sparla, Richard [VerfasserIn]
• Verfasst von: Su, Lu [VerfasserIn]
• Verfasst von: Klingmüller, Ursula [VerfasserIn]
• Verfasst von: Barz, Matthias [VerfasserIn]
• Verfasst von: Hentze, Matthias W. [VerfasserIn]
• Verfasst von: Sotillo, Rocio [VerfasserIn]
• Verfasst von: Muckenthaler, Martina [VerfasserIn]
• Titel: Superparamagnetic iron oxide nanoparticles reprogram the tumor microenvironment and reduce lung cancer regrowth after Crizotinib treatment
• Verf.angabe: Natalie K. Horvat, Sara Chocarro, Oriana Marques, Tobias A. Bauer, Ruiyue Qiu, Alberto Diaz-Jimenez, Barbara Helm, Yuanyuan Chen, Stefan Sawall, Richard Sparla, Lu Su, Ursula Klingmüller, Matthias Barz, Matthias W. Hentze, Rocío Sotillo, Martina U. Muckenthaler
• E-Jahr: 2024
• Jahr: 16 April 2024
• Umfang: 17 S.
• Fussnoten: Gesehen am 09.07.2024
• Titel Quelle: Enthalten in: American Chemical SocietyACS nano
• Ort Quelle: Washington, DC : Soc., 2007
• Jahr Quelle: 2024
• Band/Heft Quelle: 18(2024), 17, Seite 11025-11041
• ISSN Quelle: 1936-086X
• DOI: doi:10.1021/acsnano.3c08335
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 189470617X

Abstract

ALK-positive NSCLC patients demonstrate initial responses to ALK tyrosine kinase inhibitor (TKI) treatments, but eventually develop resistance, causing rapid tumor relapse and poor survival rates. Growing evidence suggests that the combination of drug and immune therapies greatly improves patient survival; however, due to the low immunogenicity of the tumors, ALK-positive patients do not respond to currently available immunotherapies. Tumor-associated macrophages (TAMs) play a crucial role in facilitating lung cancer growth by suppressing tumoricidal immune activation and absorbing chemotherapeutics. However, they can also be programmed toward a pro-inflammatory tumor suppressive phenotype, which represents a highly active area of therapy development. Iron loading of TAMs can achieve such reprogramming correlating with an improved prognosis in lung cancer patients. We previously showed that superparamagnetic iron oxide nanoparticles containing core-cross-linked polymer micelles (SPION-CCPMs) target macrophages and stimulate pro-inflammatory activation. Here, we show that SPION-CCPMs stimulate TAMs to secrete reactive nitrogen species and cytokines that exert tumoricidal activity. We further show that SPION-CCPMs reshape the immunosuppressive Eml4-Alk lung tumor microenvironment (TME) toward a cytotoxic profile hallmarked by the recruitment of CD8+ T cells, suggesting a multifactorial benefit of SPION-CCPM application. When intratracheally instilled into lung cancer-bearing mice, SPION-CCPMs delay tumor growth and, after first line therapy with a TKI, halt the regrowth of relapsing tumors. These findings identify SPIONs-CCPMs as an adjuvant therapy, which remodels the TME, resulting in a delay in the appearance of resistant tumors.