Somatic mutations associate with clonal expansion of CD8+ T cells

被引:2
|
作者
Lundgren, Sofie [1 ,2 ,3 ,4 ]
Myllymaki, Mikko [1 ,2 ,3 ,4 ]
Jarvinen, Timo [1 ,2 ,3 ,4 ,5 ,6 ]
Keraenen, Mikko A. I. [1 ,2 ,3 ,4 ,7 ]
Theodoropoulos, Jason [1 ,2 ,3 ,4 ]
Smolander, Johannes [1 ,2 ,3 ,4 ]
Kim, Daehong [1 ,2 ,3 ,4 ]
Salmenniemi, Urpu [7 ,8 ]
Walldin, Gunilla [9 ,10 ]
Savola, Paula [1 ,2 ,3 ,4 ,11 ,12 ]
Kelkka, Tiina [1 ,2 ,3 ,4 ]
Rajala, Hanna [1 ,2 ,3 ,4 ,7 ]
Hellstroem-Lindberg, Eva [2 ,9 ,10 ]
Itala-Remes, Maija [4 ,8 ]
Kankainen, Matti [1 ,2 ,3 ,4 ,5 ,6 ]
Mustjoki, Satu [1 ,2 ,3 ,4 ,13 ]
机构
[1] Univ Helsinki, Hematol Res Unit Helsinki, Helsinki, Finland
[2] Helsinki Univ Hosp Comprehens Canc Ctr, Helsinki, Finland
[3] Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland
[4] Univ Helsinki, Dept Clin Chem & hematol, Helsinki, Finland
[5] Univ Helsinki, Med & Clin Genet, Helsinki, Finland
[6] helsinki Univ Hosp, Helsinki, Finland
[7] Helsinki Univ Hosp, Comprehens Canc Ctr, Dept Hematol, Helsinki, Finland
[8] Turku Univ Hosp, Stem Cell Transplantat Unit, Turku, Finland
[9] Karolinska Inst, Ctr Hematol & Regenerat Med, Dept Med, Stockholm, Sweden
[10] Karolinska Univ Hosp, Stockholm, Sweden
[11] Helsinki Univ Hosp, HUS Diagnost Ctr, Dept Clin Chem, Helsinki, Finland
[12] Univ helsinki, Helsinki, Finland
[13] iCAN Digital Precis Canc Med Flagship, Helsinki, Finland
来源
SCIENCE ADVANCES | 2024年 / 10卷 / 23期
基金
欧洲研究理事会; 芬兰科学院;
关键词
STAT3; MUTATIONS; STEM-CELLS; HEMATOPOIESIS; INFLAMMATION; FRAMEWORK; SELECTION; CANCER; COMMON;
D O I
10.1126/sciadv.adj0787
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Somatic mutations in T cells can cause cancer but also have implications for immunological diseases and cell therapies. The mutation spectrum in nonmalignant T cells is unclear. Here, we examined somatic mutations in CD4(+) and CD8(+) T cells from 90 patients with hematological and immunological disorders and used T cell receptor (TCR) and single-cell sequencing to link mutations with T cell expansions and phenotypes. CD8(+) cells had a higher mutation burden than CD4(+) cells. Notably, the biggest variant allele frequency (VAF) of non-synonymous variants was higher than synonymous variants in CD8(+) T cells, indicating non-random occurrence. The non-synonymous VAF in CD8(+) T cells strongly correlated with the TCR frequency, but not age. We identified mutations in pathways essential for T cell function and often affected lymphoid neoplasia. Single-cell sequencing revealed cytotoxic T-EMRA phenotypes of mutated T cells. Our findings suggest that somatic mutations contribute to CD8(+) T cell expansions without malignant transformation.
引用
收藏
页数:13
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