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PD-1 阻断增强 TIL(肿瘤浸润淋巴细胞)抗三阴性乳腺癌的功能

英文原题:Augmentation of antitumor function of tumor-infiltrating lymphocytes against triple-negative breast cancer by PD-1 blockade.

查看英文原题

Augmentation of antitumor function of tumor-infiltrating lymphocytes against triple-negative breast cancer by PD-1 blockade.

PubMed 2021/12/09(内容时间) Cell Biol Int Q3 · IF 3.5(JCR 2025)

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中文摘要

基于T细胞的免疫治疗和免疫检查点阻断已成功用于治疗多种人类实体癌。本研究试图探讨过继细胞治疗联合程序性细胞死亡蛋白1(PD-1)抑制剂对三阴性乳腺癌(TNBC)的抗肿瘤作用的可行性和疗效。从TNBC小鼠肿瘤组织中分离并扩增TIL(肿瘤浸润淋巴细胞)(TILs),并将用于过继细胞治疗的TILs(TILs-ACT)与PD-1抑制剂联合应用于TNBC小鼠模型。在体外和体内评估治疗前后的抗肿瘤疗效、细胞因子分泌和病理变化。

我们发现TILs比常规T细胞表现出更高的IFN-和TNF-分泌。TILs-ACT联合PD-1抑制剂促进了活性T细胞向肿瘤组织的浸润,并在体内模型中发挥了强大的抗肿瘤作用。

此外,该策略能够下调TILs上抑制性标志物PD-1的表达。总之,PD-1阻断调节了T细胞耗竭,并与过继性TIL转移免疫治疗产生协同作用,导致已建立的TNBC肿瘤被清除。这些发现可能有助于为TNBC开发一种可行且有效的治疗策略。

展开英文摘要原文

T-cell-based immunotherapy and immune checkpoint blockade have been successfully used to treat several human solid cancers. The present study attempted to investigate the feasibility and efficacy of the antitumor effect of adoptive cell therapy along with programmed cell death protein 1 (PD-1) inhibitor on triple-negative breast cancer (TNBC).

Tumor infiltration lymphocytes (TILs) from TNBC mouse tumor tissues were isolated and expanded, and TILs for adoptive cell therapy (TILs-ACT) were applied in combination with a PD-1 inhibitor to the TNBC mouse model. The pre- and post-therapy antitumor efficacy, cytokine secretion, and pathological changes were assessed both in vitro and in vivo.

We found that TILs exhibited higher IFN- and TNF- secretion than conventional T cells. The TILs-ACT combined with PD-1 inhibitor promoted active T-cell infiltration into the tumor tissue and exerted a strong antitumor effect in an in vivo model.

Additionally, the strategy could downregulate the expression of inhibitory marker PD-1 on TILs.

In conclusion, PD-1 blockade regulated T-cell exhaustion that synergized with adoptive TIL transfer immunotherapy, leading to eradication of established TNBC tumors.

These findings might be useful in developing a feasible and effective therapeutic approach for TNBC.

论文信息

作者
Song H、Wang H、Gong M、Wu L、Liu X、Cao W、Gao X、Dou R
单位
Breast Disease Center, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.China
期刊
Cell biology international2022 Feb
原文标识
PubMed 34854515 · DOI 10.1002/cbin.11729