树突状细胞（DC）成熟刺激物质决定这些抗原呈递细胞的效力，从而影响T细胞反应的质量。我们的研究表明，通过编码CD40配体、抗原识别受体4的构成性活化变异体以及共刺激分子CD70的TriMix mRNA成熟DC可以产生抗菌转录方案。除此之外，我们还进一步证明，当TriMix中的CD70 mRNA被编码干扰素γ和诱骗性白细胞介素-10受体α的mRNA取代，形成一个称为TetraMix mRNA的四组分混合物时，树突状细胞将重定向至抗病毒转录方案。进一步的研究表明，TetraMixDCs能够高效诱导体外肿瘤抗原特异性CD8+ T细胞。肿瘤特异性抗原（TSAs）是癌症免疫疗法中新兴且有吸引力的目标。由于识别TSAs的 T-细胞受体主要存在于原始CD8+ T细胞（TN）中，因此，我们进一步探讨了TriMixDCs或TetraMixDCs刺激CD8+ TN细胞时肿瘤抗原特异性T细胞的激活情况。在两种情况下，刺激均导致CD8+ TN细胞向具有细胞毒活性的肿瘤特异性干细胞状记忆、效应记忆和中心记忆T细胞的转化。这些发现表明，TetraMix mRNA，以及它在DCs中诱导的抗病毒成熟程序，可以在癌症患者中触发抗肿瘤免疫反应。版权所有@de Mey, Locy, De Ridder, De Schrijver, Autaers, Lakdimi, Esprit, Franceschini, Thielemans, Verdonck 和Breckpot。

Dendritic cell (DC)-maturation stimuli determine the potency of these antigen-presenting cells and, therefore, the quality of the T-cell response. Here we describe that the maturation of DCs via TriMix mRNA, encoding CD40 ligand, a constitutively active variant of toll-like receptor 4 and the co-stimulatory molecule CD70, enables an antibacterial transcriptional program. Besides, we further show that the DCs are redirected into an antiviral transcriptional program when CD70 mRNA in TriMix is replaced with mRNA encoding interferon-gamma and a decoy interleukin-10 receptor alpha, forming a four-component mixture referred to as TetraMix mRNA. The resulting TetraMixDCs show a high potential to induce tumor antigen-specific T cells within bulk CD8+ T cells. Tumor-specific antigens (TSAs) are emerging and attractive targets for cancer immunotherapy. As T-cell receptors recognizing TSAs are predominantly present on naive CD8+ T cells (TN), we further addressed the activation of tumor antigen-specific T cells when CD8+ TN cells are stimulated by TriMixDCs or TetraMixDCs. In both conditions, the stimulation resulted in a shift from CD8+ TN cells into tumor antigen-specific stem cell-like memory, effector memory and central memory T cells with cytotoxic capacity. These findings suggest that TetraMix mRNA, and the antiviral maturation program it induces in DCs, triggers an antitumor immune reaction in cancer patients.Copyright © 2023 de Mey, Locy, De Ridder, De Schrijver, Autaers, Lakdimi, Esprit, Franceschini, Thielemans, Verdonck and Breckpot.