INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Di Wu,Tiancheng Gong,Zhongxiang Sun,Xihao Yao,Dongzhi Wang,Qiyang Chen,Qingsong Guo,Xiaohong Li,Yibing Guo,Yuhua Lu
The tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) is characterized by deposition of desmoplastic matrix (including collagen and hyaluronic acid). And the interactions between tumor-associated macrophages (TAMs) and tumor cells play a crucial role in progression of PDAC. Hence, the appropriate model of tumor cell-macrophage interaction within the unique PDAC TME is of significantly important. To this end, a 3D tumor niche based on dual-crosslinking gelatin methacrylate and hyaluronic acid methacrylate hydrogels was constructed to simulate the desmoplastic tumor matrix with matching compressive modulus and composition. The bionic 3D tumor niche creates an immunosuppressive microenvironment characterized by the downregulation of M1 markers and upregulation of M2 markers in TAMs. Mechanistically, RNA-seq analysis revealed that the PI3K-AKT signaling pathway might modulate the phenotypic balance and recruitment of macrophages through regulating SELE and VCAM-1. Furthermore, GO and GSEA revealed the biological process of leukocyte migration and the activation of cytokine-associated signaling were involved. Finally, the 3D tumor-macrophage niches with three different ratios were fabricated which displayed increased M2-like polarization and stemness. The utilization of the 3D tumor niche has the potential to provide a more accurate investigation of the interplay between PDAC tumor cells and macrophages within an in vivo setting.
研究领域:
癌症生物学
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组织工程
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生物材料
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免疫学
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细胞信号传导
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产品关联
DOI
PubMed
高影响因子
Science Advances
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2024
·Vol. 10
·期 13
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IF 11.7
Gongxi Qiao,Shenglin Li,Xumin Pan,Ping Xie,Ruixi Peng,Xiangrong Huang,Mengyun He,Jianhui Jiang,Xia Chu
Directly activating CD8+ T cells within the tumor through antigen-presenting cells (APCs) hold promise for tumor elimination. However, M2-like tumor-associated macrophages (TAMs), the most abundant APCs in tumors, hinder CD8+ T cell activation due to inefficient antigen cross-presentation. Here, we demonstrated a personalized nanotherapeutic platform using surgical tumor–derived galactose ligand–modified cancer cell membrane (CM)–coated cysteine protease inhibitor (E64)–loaded mesoporous silica nanoparticles for postsurgical cancer immunotherapy. The platform targeted M2-like TAMs and released E64 within lysosomes, which reshaped antigen cross-presentation and directly activated CD8+ T cells, thus suppressing B16-OVA melanoma growth. Furthermore, this platform, in combination with anti–PD-L1 antibodies, enhanced the therapeutic efficacy and substantially inhibited 4T1 tumor growth. CMs obtained from surgically resected tumors were used to construct a personalized nanotherapeutic platform, which, in synergy with immune checkpoint blockade (ICB), effectively inhibited postsurgical tumor recurrence in 4T1 tumor. Our work offered a robust, safe strategy for cancer immunotherapy and prevention of postsurgical tumor recurrence.
研究领域:
癌症免疫疗法
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纳米技术
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免疫学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
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2023
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IF 13.3
Tianze Jiang,Bingjie Wang,Teng Wang,Lianxiao Zhang,Xiangyan Chen,Xia Zhao
Immunotherapy is regarded as a prospective strategy against metastatic cancer. However, tumor-associated macrophages (TAMs), which accumulate in hypoxic tumor microenvironment, reduce the effectiveness of immunotherapy by blocking or “hijacking” the initiation of the immune response. Here, a novel tumor-targeted nanoplatform loaded with hypoxia-pathway-intervened docosahexaenoic acid (DHA) and chemotherapeutic drug carfilzomib (CFZ) is developed, which realizes the rescue of TAM-hijacked immune response and effective metastatic cancer immunotherapy. DHA is conjugated to fucoidan (Fuc) via a reduction cleavable selenylsulfide bond (SSe) for micelle preparation, and CFZ is encapsulated in the hydrophobic cores of micelles. The functionalized nanoplatforms (Fuc─SSe─DHA (FSSeD)–CFZs) induce immunogenic cell death, inhibit hypoxia-inducible factor-1α expression, and improve immunosuppression by TAM suppression. FSSeD–CFZs enhance immune response against primary tumor development and metastasis formation. In brief, the novel rescue strategy for TAM-hijacked immunoreaction by inhibiting hypoxia pathway has the potential and clinically translational significance for enhanced metastatic cancer immunotherapy.
研究领域:
癌症免疫治疗
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药学
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纳米技术
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
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2020
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IF 10.317
Jing Wang,Yanzhou Chang,Hui Luo,Wenxiao Jiang,Ligeng Xu,Tianfeng Chen,Xueqiong Zhu
Low tumor mutational burden and absence of T cells within the tumor sites are typical characteristics of “cold immune tumors” that paralyzes the immune system. The strategy of reversing “cold tumors” to “hot tumors” infiltrated high degree of T cells in order to activate anti-tumor immunity has attracted lots of attentions. Herein, immunogenic core–shell [email protected] NPs is fabricated by gold-selenium coordination bond to realize nanoparticles-mediated local photothermal-triggered immunotherapy. As expected, incorporation of gold nanostars (AuNSs) with improved photothermal stability and conversion efficiency promotes the disintegration and transformation of selenium nanoparticles (SeNPs), thus leading to enhanced cancer cells apoptosis by producing higher hyperthermia. Moreover, the results of in vivo experiments demonstrate that the synergy between SeNPs-mediated chemotherapy and AuNSs-induced photothermal therapy not only generated a localized antitumor-immune response with excellent cancer killing effect under the presence of tumor-associated antigens, but also effectively reprogrammed the tumor associated macrophages (TAMs) from M2 to M1 phenotype with tumoricidal activity to devour distant tumors. Without a doubt, this study not only provides a potent strategy to reverse the immunosuppressive tumor microenvironment , but also offers a new insight for potential clinical application in tumor immunotherapy.
研究领域:
纳米技术
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免疫疗法
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肿瘤学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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