CD8型
细胞毒性T细胞
CD3型
癌症研究
淋巴细胞
T细胞
免疫学
免疫系统
外周血单个核细胞
流式细胞术
T淋巴细胞
外周血淋巴细胞
医学
病理
免疫分型
单克隆抗体
免疫疗法
作者
Tiepeng Li,Lingdi Zhao,Yonghao Yang,Yao Wang,Yong Zhang,Guo Jindong,Guangyu Chen,Peng Qin,Benling Xu,Baozhen Ma,Fang Zhang,Yiman Shang,Qingjun Li,Kai Zhang,Dongfeng Yuan,Chaojie Feng,Yan Ma,Zhiyong Liu,Zhichao Tian,Hongle Li,Shengdian Wang,Quanli Gao
出处
期刊:Cancer Research
[American Association for Cancer Research]
日期:2021-04-15
卷期号:81 (8): 2184-2194
被引量:3
标识
DOI:10.1158/0008-5472.can-20-2300
摘要
Both tumor-infiltrating lymphocytes (TIL) and PD-1+ peripheral blood lymphocytes (PBL) are enriched for tumor-reactive clones recognizing known and unknown tumor antigens. However, the relationship between the T-cell receptor-β (TCRβ) repertoires of the TILs and T cells expanded from paired PD-1+ PBLs, and whether T cells expanded from PD-1+ PBLs can be used to treat patients with cancer as TIL substitutes remain unclear. Here, we established a highly efficient protocol to prepare polyclonal T cells from PD-1+ PBLs. A functional T-cell assay and tetramer staining revealed that cells from PD-1+ PBLs were relatively enriched for tumor-reactive T cells. Furthermore, deep TCRβ sequencing data revealed that an average of 11.29% (1.32%-29.06%; P = 0.015; n = 8) tumor-resident clonotypes were found in T cells expanded from paired PD-1+ PBLs, and the mean accumulated frequency of TIL clones found in T cells expanded from PD-1+ PBLs was 35.11% (7.23%-78.02%; P = 0.017; n = 8). Moreover, treatment of four patients, who failed multiline therapy and developed acquired resistance to anti-PD-1, with autologous T cells expanded from PD-1+ PBLs combined with anti-PD-1 antibody elicited objective responses from three of them. These results indicate that T cells expanded from PD-1+ PBLs share more clones with paired TILs and could be used to treat patients with cancer as TIL substitutes. SIGNIFICANCE: This study harnesses the tumor reactivity of PD-1+ PBLs, developing a method to expand T cells from these clones as a potential therapeutic strategy and TIL substitute in patients with cancer.See related commentary by Ladle, p. 1940.
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