Zhang et al employed cytotoxic B-elemene (ELE)-treated dying cancer cells (DCCs) as an immunogenic cell source within a sprayable fibrin hydrogel (with additional ELE). In a 4T1 orthotopic partial resection model, the gel controlled primary and untreated distal tumor growth, increasing the M1:M2 macrophage ratio, and activated CD103+ DCs. The gel increased T cell frequency in the tumor, lymph nodes, and spleen, Tcm polarization, and stimulatory cytokines. Proteomics profiling of tumor fluid and plasma revealed differential expression of clinically prognostic proteins and pathways related to apoptosis, immune function, and metastasis.
Contributed by Morgan Janes
ABSTRACT: Postsurgical tumor recurrence remains a major challenge, primarily driven by the resurgence of residual microtumors at surgical margins. The tumor microenvironment (TME) in these regions plays a decisive role in treatment outcomes. Here, we present an in situ sprayed fibrin hydrogel system that integrates chemically engineered homologous dying cancer cells (DCCs) as a sustained antigen reservoir with the anticancer agent β-elemene (ELE) to enhance anti-tumor immune responses and suppress local tumor recurrence. This immunotherapeutic hydrogel (DCCs@ELE@Gel) modulates the TME by promoting a favorable M1/M2 tumor-associated macrophage balance, facilitating dendritic cell maturation, and enhancing the cross-priming of cytotoxic T cells, collectively preventing tumor regrowth. Additionally, comprehensive proteomic analysis reveals key mechanisms linking the chemo-immunotherapeutic hydrogel to tumor recurrence suppression. Our findings introduce an approach that leverages engineered tumor cells within a hydrogel matrix for improved cancer immunotherapy, offering a versatile strategy for postsurgical tumor management.
Author Info: 1- Zhejiang Provincial Key Laboratory of Ophthalmology, Zhejiang Provincial Clinical Research Center for Eye Diseases, Zhejiang Provincial Engineering Institute on Eye Diseases, Ey
Author Info: 1- Zhejiang Provincial Key Laboratory of Ophthalmology, Zhejiang Provincial Clinical Research Center for Eye Diseases, Zhejiang Provincial Engineering Institute on Eye Diseases, Eye Center of Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China
2- Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou 311121, China
3- Center for Nanomedicine and Department of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
4- School of Pharmacy, Hangzhou Normal University, Hangzhou 311121, China
5- Lead contact
