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骨髓来源肿瘤特异性 CD8(+) T 细胞较 TIL(肿瘤浸润淋巴细胞)抵抗耗竭并在荷瘤宿主中表现出更强持久性

英文原题:Tumor-Specific CD8(+) T Cells from the Bone Marrow Resist Exhaustion and Exhibit Increased Persistence in Tumor-Bearing Hosts as Compared to Tumor Infiltrating Lymphocytes.

查看英文原题

Tumor-Specific CD8(+) T Cells from the Bone Marrow Resist Exhaustion and Exhibit Increased Persistence in Tumor-Bearing Hosts as Compared to Tumor Infiltrating Lymphocytes.

PubMed 2023/08/29(内容时间) bioRxiv

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中文摘要

肿瘤特异性骨髓CD8+ T细胞可能为过继细胞治疗提供一种具有持久抗肿瘤能力的细胞来源。与TIL(肿瘤浸润淋巴细胞)相比,骨髓中的肿瘤特异性CD8+ T细胞较少呈现耗竭表型,并具有更高的持续性。骨髓细胞群富含记忆样T细胞,表现出更好的效应功能、持久性和肿瘤浸润能力。研究结果表明,骨髓可作为获取肿瘤特异性T细胞的潜在来源,用于开发过继细胞治疗。

展开英文摘要原文

Immunotherapy is now an integral aspect of cancer therapy. Strategies employing adoptive cell therapy (ACT) have seen the establishment of chimeric antigen receptor (CAR)-T cells using peripheral blood lymphocytes as well as tumor infiltrating lymphocytes (TILs) with significant clinical results.

Despite these successes, the limitations of the current strategies are also emerging and novel approaches are needed. The bone marrow (BM) is an immunological niche that houses T cells with specificity for previously encountered antigens, including tumor-associated antigens from certain solid cancers.

This study sought to improve our understanding of tumor-specific BM T cells in the context of solid tumors by comparing them with TILs, and to assess whether there is a rationale for using the BM as a source of T cells for ACT against solid malignancies.

Herein, we demonstrate that T cells from the BM appear superior to TILs as a source of cells for cellular therapy. Specifically, they possess a memory-enriched phenotype and exhibit improved effector function, greater persistence within a tumor-bearing host, and the capacity for increased tumor infiltration. Taken together, these data provide a foundation for further exploring the BM as a source of tumor-specific T cells for ACT in solid malignancies.

论文信息

作者
Zawidzka EM、Biavati L、Thomas A、Zanettini C、Marchionni L、Leone R、Borrello I
单位
Johns Hopkins University School of Medicine, Bloomberg Kimmel Institute for Cancer Immunotherapy.
文献类型
预印本
期刊
bioRxiv : the preprint server for biology2023 Aug 29
原文标识
PubMed 37693379 · DOI 10.1101/2023.08.28.555119