In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 8 ( 2021-04-15), p. 2184-2194
Abstract:
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
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/0008-5472.CAN-20-2300
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2021
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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