American Association for Cancer Research
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Figure S7 from T Cells Expanded from PD-1+ Peripheral Blood Lymphocytes Share More Clones with Paired Tumor-Infiltrating Lymphocytes

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posted on 2023-03-31, 04:42 authored by Tiepeng Li, Lingdi Zhao, Yonghao Yang, Yao Wang, Yong Zhang, Jindong Guo, 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

The accumulative frequency of shared TIL clones in TCR-β repertoire of PD-1+ T from patient MM-4 before and after in vitro expansion.


National Natural Science Foundation of China

Henan Medical Science and Technique Foundation

Henan Provincial Scientific and Technological Project



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. 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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