Tumor-derived autophagosome vaccines combined with immune adjuvants mediate antitumor immune responses via the neoantigen pathway.

IF 2 4区 医学 Q3 ONCOLOGY Neoplasma Pub Date : 2023-12-01 Epub Date: 2023-11-28 DOI:10.4149/neo_2023_230125N41
Jia Yuan, Yue Chang, Yalan Dai, Yutong Chen, Rongbin Yue, Linjuan Zeng
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Abstract

Vaccines composed of autophagosomes derived from tumor cells called DRibbles (DRiPs-containing blebs) are involved in the cross-presentation of tumor antigens, thus inducing cross-reactive T-cell responses against the tumor. Compared with traditional tumor lysate vaccines, autophagosome vaccines were found to be better sources of multiple tumor-associated antigens (TAAs) that activate antigen-specific T-cells. However, the involvement of tumor neoantigens in the immune responses of autophagosome vaccines remains unclear. The present study showed that exogenous autophagosome vaccines (DRibbles) combined with immune adjuvants (anti-OX40 antibody and ATP) can effectively activate functional T cells in vitro. Importantly, the combination of exogenous tumor-derived autophagosome vaccines and immune adjuvants was found to induce tumor regression in B16F10 and 4T1 tumor-bearing mice. The combination of autophagosome-enriched DRibbles with anti-OX40 antibody and ATP also exhibited optimal immune stimulation and antitumor efficiency in vivo. The effectiveness of exogenous DRibble vaccines was mainly due to their enhancement of tumor immunogenicity by increasing the presentation and release of tumor neoantigens. These findings suggest that this immunotherapeutic method may be effective in the treatment of cancer.

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肿瘤源性自噬体疫苗联合免疫佐剂通过新抗原途径介导抗肿瘤免疫反应。
由来自肿瘤细胞的自噬小体组成的疫苗称为DRibbles(含有drips的气泡),参与肿瘤抗原的交叉呈递,从而诱导针对肿瘤的交叉反应性t细胞应答。与传统的肿瘤裂解物疫苗相比,自噬体疫苗被发现是激活抗原特异性t细胞的多种肿瘤相关抗原(TAAs)的更好来源。然而,肿瘤新抗原在自噬体疫苗免疫应答中的作用尚不清楚。本研究表明外源性自噬小体疫苗(DRibbles)联合免疫佐剂(抗ox40抗体和ATP)可在体外有效激活功能性T细胞。重要的是,外源性肿瘤源性自噬体疫苗和免疫佐剂的组合被发现可诱导B16F10和4T1荷瘤小鼠的肿瘤消退。富含自噬体的DRibbles与抗ox40抗体和ATP的组合在体内也表现出最佳的免疫刺激和抗肿瘤效果。外源性DRibble疫苗的有效性主要是由于其通过增加肿瘤新抗原的呈递和释放来增强肿瘤免疫原性。这些发现表明,这种免疫治疗方法可能有效地治疗癌症。
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来源期刊
Neoplasma
Neoplasma 医学-肿瘤学
CiteScore
5.40
自引率
0.00%
发文量
238
审稿时长
3 months
期刊介绍: The journal Neoplasma publishes articles on experimental and clinical oncology and cancer epidemiology.
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