Akademik Veri Yönetim Sistemi
Büyüker A. (Yürütücü), Kasap M., Sarıhan M., Karadenizli A.
TÜBİTAK Projesi, 3501 - Ulusal Genç Araştırmacı Kariyer Geliştirme Programı, 2025 - 2027
Colorectal cancer (CRC) is a major global health problem with increasing incidence rates and an urgent need for innovative therapies. Immunotherapy studies on CRC reprogram tumor-associated macrophages (TAMs) to enhance anticancer functions by activating immunity. This reprogramming aims to redirect TAMs from the anti-inflammatory M2 phenotype, which promotes tumor growth, to the pro-inflammatory M1 phenotype. There are various manipulation methods in the literature to polarize macrophages to the M1 phenotype. One of these methods, activation of toll-like receptors (TLRs), has the advantages of having a cell-specific effect and being a method that does not interfere with the genetic structure. Although clinical trials with immunotherapy strategies using TLR agonists have been applied in various cancer treatments in recent years, significant results have not yet been achieved in CRC treatment. Therefore, the aim of this study was to manipulate cancer-derived monocytes and TAMs to M1 phenotype using candidate TLR7/8 and TLR4 agonists selected from the literature, respectively, and to evaluate their antitumor activity against 3D CRC spheroid cells in a coculture model by advanced protein analysis in vitro. 3D spheroid constructs were preferred in tumor modeling studies because they are important cell models that mimic primary tissue with high efficiency.