Biology subjects

Raykowski, B.

Publications and source records attributed to Raykowski, B..

2 recordsLinked to original sources

bioRxiv2026

Transcription Factor-Mediated Reprogramming of Cancer-Associated Fibroblasts Reveals Targetable Vulnerabilities in Solid Tumors

Cancer-associated fibroblasts (CAFs) contribute to immune exclusion and therapy resistance in solid tumors, limiting the efficacy of chimeric antigen receptor (CAR) T cell and immune cell therapy. To overcome this, we developed a transcription factor (TF)-based strategy to reprogram prostate-derived CAFs (pCAFs) into normal fibroblast-like cells (NFs). We prioritized TFs enriched in quiescent stellate cells--Vitamin D receptor (VDR), Peroxisome Proliferator-Activated Receptor gamma (PPAR{gamma}), and p53--and selected VDR for proof-of-concept studies. Lentiviral VDR expression in pCAFs produced VDR-reprogrammed NFs (VDR-rpNFs) with reduced CAF markers, increased ATP, and suppressed TGF-{beta} and IL6, indicating phenotypic and metabolic reversion. In both in vitro 3D co-cultures and in vivo, VDR-rpNFs disrupted tumor architecture, enhanced CAR T cell infiltration, and reduced necrosis. PPAR{gamma}- and p53-rpNFs showed similar reprogramming effects. These results suggest TF-guided fibroblast reprogramming as a viable strategy to remodel the tumor microenvironment and improve CAR T cell efficacy in solid tumors.

cancer biology↗

bioRxiv2024

Combining Top-Down and Bottom-Up: An Open Microfluidic Microtumor Model for Investigating Tumor Cell-ECM Interaction and Anti-Metastasis

Using a combined top-down (i.e., operator-directed) and bottom-up (i.e., cell-directed) strategy, we present an Under-oil Open Microfluidic System (UOMS)-based microtumor model for investigating tumor cell migration and anti-metastasis drug test. Compared to the mainstream closed microfluidics-based microtumor models, the UOMS microtumor model features: i) micrometer-scale lateral resolution of surface patterning with open microfluidic design for flexible spatiotemporal sample manipulation (i.e., top-down); ii) self-organized extracellular matrix (ECM) structures and tumor cell-ECM spontaneous remodeling (i.e., bottom-up); and iii) free physical access to the samples on a device with minimized system disturbance. The UOMS microtumor model is used to test an anti-metastasis drug (incyclinide, aka CMT-3) with a triple negative breast cancer cell line (MDA-MB-231). The in vitro results show a suppression of tumor cell migration and ECM remodeling echoing with the in vivo mice metastasis results.

bioengineering↗