CD20 targeted nanomedicine enhances anti-tumor immunity in diffuse large B-cell lymphoma by activating cGAS/STING pathway.

Authors

Zuofei Chi, Nannan Xu, Ying Sun, Bin Zhang, Ye Wang, Jiayuan Chen, Cen Meng, Zehui Jiang, Chunyang Tian, Ruowen Sun

Published in

Cancer letters. Pages 218850. Sep 19, 2026. Epub Sep 19, 2026.

Abstract

Despite the emergence of immunotherapies, the treatment of diffuse large B-cell lymphoma (DLBCL) remains challenging. This is mainly attributed to the immunosuppressive properties of the tumor microenvironment (TME), which limit the achievement of durable therapeutic responses. High expression of Polo-like kinase 4 (PLK4), a mitotic kinase, is associated with significantly poorer survival outcomes in DLBCL patients receiving CHOP-based chemotherapy. Moreover, the combination of mitotic kinase inhibitors and the microtubules-targeting agent vincristine (VCR) exhibit synergistic anti-tumor effects in B-cell lymphoma mouse models. In this study, we found that PLK4 was up-regulated in DLBCL, and its silencing significantly inhibited tumor growth. Furthermore, the combination of si-PLK4 and VCR exerted stronger anti-tumor effects than either treatment alone, which was mediated by activating cGAS-STING pathway. Based on these findings, we developed a nanomedicine-based therapeutic strategy for DLBCL using zeolite imidazole framework (ZIF)-90 as carrier for co-delivery of VCR and si-PLK4. To enhance targeting specificity toward CD20⁺ lymphoma cells, rituximab (RTX) was conjugated onto the nanomedicine, named VCR/siPLK4@ZIF-90-RTX. The VCR/siPLK4@ZIF-90-RTX showed minimal premature release of VCR and siPLK4, with a pH-responsive release profile. Compared with the combination of VCR and RTX, VCR/siPLK4@ZIF-90-RTX showed enhanced anti-tumor effects in vitro, and exhibited high biocompatibility and low toxic side effects in vivo. Moreover, VCR/siPLK4@ZIF-90-RTX could promote the maturation of dendritic cells and subsequent tumor infiltration of CD8⁺ T and CD4⁺ T cells by activating cGAS-STING pathway. Collectively, this work provides a potential synergistic chemo-immunotherapeutic strategy that effectively remodels the immunosuppressive TME and improves therapeutic efficacy.

PMID:
42762966
Bibliographic data and abstract were imported from PubMed on 20 Sep 2026.

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