Comparison of tumor-derived total RNA and cell lysate on antitumor immune activity
Comparison of tumor-derived total RNA and cell lysate on antitumor immune activity
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DOI：
10.1016/j.biopha.2023.114377
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发表时间：
2023-02-08
影响因子：
7.5
通讯作者：
Lin，Jiahao
中科院分区：
文献类型：
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作者：
Chen，Qi;Jin，Yipeng;Lin，Jiahao
肿瘤来源的总RNA（TdRNA）和细胞裂解物（TCL），与几乎所有的相关肿瘤抗原，代表有吸引力的替代来源的抗原在抗肿瘤免疫治疗。然而，它们引发针对乳腺癌的免疫应答的能力的比较仍然缺乏。本研究系统比较了TdRNA和TCL的抗肿瘤免疫作用。我们从4T1小鼠乳腺癌细胞中分离TdRNA和TCL，发现这两种抗原来源可以在细胞和体内水平刺激树突状细胞（DC）的成熟，并诱导强大的细胞免疫应答，如腹股沟淋巴结和脾脏中CD4+和CD8+T细胞百分比增加所证明的。但TdRNA通过激活DCs增加T细胞数量的作用强于TCL。此外，在小鼠4T1肿瘤模型中进一步评估紫杉醇（PTX）分别与TdRNA和TCL的协同抗肿瘤功效。与TCL相比，TdRNA与PTX联合应用能更有效地抑制肿瘤生长，且全身毒性较低，这可能与TdRNA能改善全身免疫功能，促进肿瘤免疫浸润有关。总体而言，TdRNA在抗肿瘤免疫方面优于TCL，有望成为应用于肿瘤抗原来源的有希望的候选者。
Tumor-derived total RNA (TdRNA) and cell lysate (TCL), with almost all the relevant tumor antigens, represent attractive alternative sources of antigens in antitumor immunotherapy. However, the comparison of their capacity to elicit immune responses against breast cancer is still lacking. In this study, the antitumor immune effects of TdRNA and TCL were systematically compared. We isolated TdRNA and TCL from 4T1 mouse breast cancer cells, and found that both sources of antigens could stimulate the maturation of dendritic cells (DCs) at the cellular and in vivo levels, and induce robust cellular immune responses, as evidenced by the increased percentages of both CD4+and CD8+T cells in the inguinal lymph nodes and spleen. But TdRNA performed stronger immunoactivities than TCL on the increase of T cell population through DCs activation. Additionally, the synergistic antitumor efficacy of paclitaxel (PTX) with TdRNA and TCL respectively was further evaluated in the murine 4T1 tumor model. Compared with TCL, TdRNA could inhibit tumor growth more effectively with low systemic toxicity when combined with PTX, which was, at least in part, attributable to the improvement of systemic immune function and tumor immune infiltration. Overall, TdRNA outperforms TCL in antitumor immunity, and is expected to be a promising candidate for application as the source of tumor antigens.