RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Thermosensitive hydrogel delivery of BCG lysates and tumor antigens: A novel strategy for melanoma immunoprevention and therapeutics.
Thermosensitive hydrogel delivery of BCG lysates and tumor antigens: A novel strategy for melanoma immunoprevention and therapeutics.
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黑色素瘤被认为是最具侵袭性的皮肤癌之一,其全球发病率持续稳步上升。尽管卡介苗(BCG)已被确定为黑色素瘤的一种潜在病灶内治疗方法,但其治疗效果仍不理想。本研究介绍了一种新型温敏水凝胶,该水凝胶由BCG裂解物与OVA肽或肿瘤细胞裂解物配制而成(PPP-BCG-OVA/TL)。该水凝胶能够引发强烈的全身性肿瘤抗原特异性T细胞反应,并显著增强CD45+白细胞、巨噬细胞、CD8+ T细胞和自然杀伤(NK)细胞向肿瘤微环境的浸润。因此,在预防性和治疗性情境下,PPP-BCG-OVA/TL水凝胶疫苗接种有效抑制了皮下黑色素瘤小鼠模型中的肿瘤生长并延长了生存期。这些发现凸显了通过添加肿瘤抗原以及使用基于水凝胶的递送平台来显著提高BCG裂解物治疗效果的潜力。
Melanoma, recognized as one of the most aggressive forms of skin cancer, continues to show a steady rise in global incidence. While Bacillus Calmette-Guérin (BCG) has been identified as a potential intralesional therapy for melanoma, its therapeutic efficacy remains suboptimal.
This study introduces a novel thermosensitive hydrogel formulated with BCG lysates and either OVA peptide or tumor cell lysates (PPP-BCG-OVA/TL). The hydrogel demonstrated the ability to elicit a robust systemic tumor antigen-specific T cell response and significantly enhanced the infiltration of CD45 + leukocytes, macrophages, CD8 + T cells, and natural killer (NK) cells into the tumor microenvironment.
As a result, vaccination with PPP-BCG-OVA/TL hydrogel effectively inhibited tumor growth and extended survival in mouse models of subcutaneous melanoma in both preventive and therapeutic contexts.
These findings highlight the potential to markedly improve the therapeutic efficacy of BCG lysates through the addition of tumor antigens and the use of a hydrogel-based delivery platform.
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