Ex vivo enhancement of CD8+ T cell activity using functionalized hydrogel encapsulating tonsil-derived lymphatic endothelial cells

使用功能化水凝胶包裹扁桃体来源的淋巴管内皮细胞体外增强 CD8+ T 细胞活性

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作者:Heesun Hong, Chan Hum Park, Ji Seung Lee, Kyunghee Kim, Sudarshini Nath, Moon Sik Oh, Sol Kim, Chul Hee Lee, Ki Hyun Kim, Woo Hee Choi, Kyu Young Choi, Hae Sang Park, Ok Joo Lee, In-Sun Hong, Soon Hee Kim

Conclusions

These findings suggest that the GH-GMA hydrogel, combined with anti-CD28, IL-2, VEGF-C, and T-LEC spheroids, enhances T cell activity, presenting a promising platform for cancer immunotherapies and modulation of the suppressive tumor microenvironment.

Methods

We characterized tonsil mesenchymal stem cells (TMSCs), lymphatic endothelial cells (T-LECs), stimulated T-CD8+ T cells (STCs), and GH-GMA biomaterials. The 10% 5:1 GH-GMA hydrogel, loaded with anti-CD28, cytokines interleukin-2 (IL-2) and vascular endothelial growth factor C (VEGF-C), forms a functional hydrogel capable of releasing these immune-stimulating factors. T-LEC spheroids, derived from tonsil mesenchymal stem cells (TMSCs), were encapsulated within the hydrogel to act as antigen-presenting cells for T cells.

Results

Co-encapsulation of STCs and T-LEC spheroids in the functional hydrogel resulted in significant expansion and enrichment of STCs during cultivation. Moreover, when cancer cells were co-encapsulated with STCs and T-LECs, there was increased migration of STCs towards the cancer cells and elevated expression of PD-L1 on the cancer cells. Conclusions: These findings suggest that the GH-GMA hydrogel, combined with anti-CD28, IL-2, VEGF-C, and T-LEC spheroids, enhances T cell activity, presenting a promising platform for cancer immunotherapies and modulation of the suppressive tumor microenvironment.

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