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胸恶性肿瘤的过继细胞疗法。

Adoptive cell therapies in thoracic malignancies.

机构信息

Medical and Thoracic Oncology Department, Hopital Avicenne, AP-HP, Bobigny, France.

Faculty of Medicine, University of Paris, Paris, France.

出版信息

Cancer Immunol Immunother. 2022 Sep;71(9):2077-2098. doi: 10.1007/s00262-022-03142-3. Epub 2022 Feb 7.

Abstract

Immunotherapy has gained great interest in thoracic malignancies in the last decade, first in non-small cell lung cancer (NSCLC), but also more recently in small-cell lung cancer (SCLC) and malignant pleural mesothelioma (MPM). However, while 15-20% of patients will greatly benefit from immune checkpoint blockers (ICBs), a vast majority will rapidly exhibit resistance. Reasons for this are multiple: non-immunogenic tumors, immunosuppressive tumor microenvironment or defects in immune cells trafficking to the tumor sites being some of the most frequent. Current progress in adoptive cell therapies could offer a way to overcome these hurdles and bring effective immune cells to the tumor site. In this review, we discuss advantages, limits and future perspectives of adoptive cell therapy (ACT) in thoracic malignancies from lymphokine-activated killer cells (LAK), cytokine-induced killer cells (CIK), natural killer cells (NK), dendritic cells (DC) vaccines and tumor-infiltrating lymphocytes (TILs) to TCR engineering and CARs. Trials are still in their early phases, and while there may still be many limitations to overcome, a combination of these different approaches with ICBs, chemotherapy and/or radiotherapy could vastly improve the way we treat thoracic cancers.

摘要

在过去的十年中,免疫疗法在胸部恶性肿瘤中引起了极大的兴趣,首先是在非小细胞肺癌(NSCLC)中,但最近也在小细胞肺癌(SCLC)和恶性胸膜间皮瘤(MPM)中。然而,尽管 15-20%的患者将从免疫检查点抑制剂(ICBs)中大大受益,但绝大多数患者将迅速产生耐药性。原因有很多:非免疫原性肿瘤、免疫抑制性肿瘤微环境或免疫细胞向肿瘤部位转移的缺陷是最常见的原因之一。目前在过继细胞疗法方面的进展可能提供了一种克服这些障碍的方法,并将有效的免疫细胞带到肿瘤部位。在这篇综述中,我们讨论了过继细胞疗法(ACT)在胸部恶性肿瘤中的优势、局限性和未来前景,包括淋巴因子激活的杀伤细胞(LAK)、细胞因子诱导的杀伤细胞(CIK)、自然杀伤细胞(NK)、树突状细胞(DC)疫苗和肿瘤浸润淋巴细胞(TIL),以及 TCR 工程和 CARs。试验仍处于早期阶段,尽管仍有许多限制需要克服,但将这些不同方法与 ICBs、化疗和/或放疗相结合,可能会极大地改善我们治疗胸部癌症的方式。

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