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:Multiparametric flow cytometry to characterize vaccine-induced polyfunctional T cell responses and T cell/NK cell exhaustion and memory phenotypes in mouse immuno-oncology models.
Multiparametric flow cytometry to characterize vaccine-induced polyfunctional T cell responses and T cell/NK cell exhaustion and memory phenotypes in mouse immuno-oncology models.
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在临床前癌症模型中评估癌症疫苗体内免疫原性和治疗效力的适当方法,对于克服现有疫苗局限并提高临床应用价值至关重要。特别需要能够表征针对内源性肿瘤抗原的T细胞反应的方法,以评估疫苗效力并优化抗原配方;多参数分析深入刻画肿瘤及治疗引起的免疫调节,也有助设计基于机制的联合免疫疗法。本文介绍一种通用多参数流式细胞术方法:在短期体外再刺激后,根据多种常见小鼠品系相关肿瘤表位诱导的多细胞因子产生,评估肿瘤抗原特异性CD4和CD8 T细胞反应的多功能性。作者还报告开发并应用两套21色流式面板,全面表征小鼠T细胞和NK细胞耗竭及记忆表型,尤其适用于临床前癌症模型。
Suitable methods to assess in vivo immunogenicity and therapeutic efficacy of cancer vaccines in preclinical cancer models are critical to overcome current limitations of cancer vaccines and enhance the clinical applicability of this promising immunotherapeutic strategy. In particular, availability of methods allowing the characterization of T cell responses to endogenous tumor antigens is required to assess vaccine potency and improve the antigen formulation.
Moreover, multiparametric assays to deeply characterize tumor-induced and therapy-induced immune modulation are relevant to design mechanism-based combination immunotherapies.
Here we describe a versatile multiparametric flow cytometry method to assess the polyfunctionality of tumor antigen-specific CD4 + and CD8 + T cell responses based on their production of multiple cytokines after short-term ex vivo restimulation with relevant tumor epitopes of the most common mouse strains.
We also report the development and application of two 21-color flow cytometry panels allowing a comprehensive characterization of T cell and natural killer cell exhaustion and memory phenotypes in mice with a particular focus on preclinical cancer models.
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