PMID- 37327346
OWN - NLM
STAT- MEDLINE
DCOM- 20230619
LR  - 20231124
IS  - 2375-2548 (Electronic)
IS  - 2375-2548 (Linking)
VI  - 9
IP  - 24
DP  - 2023 Jun 16
TI  - Cord blood-derived V(delta)2(+) and V(delta)2(-) T cells acquire differential cell state 
      compositions upon in vitro expansion.
PG  - eadf3120
LID - 10.1126/sciadv.adf3120 [doi]
LID - eadf3120
AB  - Human cord blood-derived gammadelta T cells (CB(gammadelta)) display a highly diverse TCR(gammadelta) 
      repertoire and have a unique subtype composition different from fetal or adult 
      peripheral blood counterparts. We expanded CB(gammadelta) in vitro using an irradiated 
      Epstein-Barr virus-transformed feeder cell-based modified rapid expansion 
      protocol (REP). Single-cell RNA sequencing tracked progressive differentiation of 
      naive CB(gammadelta) into cells expressing neoantigen-reactive tumor-infiltrating 
      lymphocyte as well as tissue-resident memory precursor-like and 
      antigen-presenting cell-like gene signatures. TCR(gammadelta) clonal tracing revealed a 
      bias toward cytotoxic effector differentiation in a much larger proportion of 
      V(delta)2(-) clones compared to V(delta)2(+) clones, resulting in the former being more 
      cytotoxic at the population level. These clonotype-specific differentiation 
      dynamics were not restricted to REP and were recapitulated upon secondary 
      nonviral antigen stimulations. Thus, our data showed intrinsic cellular 
      differences between major subtypes of human gammadelta T cells already in operation at 
      early postnatal stage and highlighted key areas of consideration in optimizing 
      cell manufacturing processes.
FAU - Ng, Jeremy Wee Kiat
AU  - Ng JWK
AUID- ORCID: 0000-0001-8663-5936
AD  - Department of Molecular Pathology, Translational Pathology Centre, Singapore 
      General Hospital, Singapore, Singapore.
FAU - Tan, Kar Wai
AU  - Tan KW
AD  - Department of Clinical Translational Research, Singapore General Hospital, 
      Singapore, Singapore.
AD  - Tessa Therapeutics Ltd, Singapore, Singapore.
FAU - Guo, Dian Yan
AU  - Guo DY
AD  - Department of Haematology, Singapore General Hospital, Singapore, Singapore.
FAU - Lai, Joey Jia Hui
AU  - Lai JJH
AD  - Department of Haematology, Singapore General Hospital, Singapore, Singapore.
FAU - Fan, Xiubo
AU  - Fan X
AUID- ORCID: 0000-0002-9479-6913
AD  - Department of Clinical Translational Research, Singapore General Hospital, 
      Singapore, Singapore.
FAU - Poon, Zhiyong
AU  - Poon Z
AD  - Department of Clinical Translational Research, Singapore General Hospital, 
      Singapore, Singapore.
AD  - Critical Analytics for Manufacturing Personalized-Medicine, Singapore-MIT 
      Alliance for Research and Technology, Singapore, Singapore.
FAU - Lim, Tse Hui
AU  - Lim TH
AUID- ORCID: 0000-0002-8733-4155
AD  - Department of Molecular Pathology, Cytogenetics Laboratory, Singapore General 
      Hospital, Singapore, Singapore.
FAU - Lim, Alvin Soon Tiong
AU  - Lim AST
AD  - Department of Molecular Pathology, Cytogenetics Laboratory, Singapore General 
      Hospital, Singapore, Singapore.
FAU - Lim, Tony Kiat Hon
AU  - Lim TKH
AUID- ORCID: 0000-0003-0645-5164
AD  - Department of Molecular Pathology, Translational Pathology Centre, Singapore 
      General Hospital, Singapore, Singapore.
FAU - Hwang, William Ying Khee
AU  - Hwang WYK
AUID- ORCID: 0000-0003-0143-6263
AD  - Department of Haematology, Singapore General Hospital, Singapore, Singapore.
AD  - National Cancer Centre Singapore, Singapore, Singapore.
FAU - Li, Shang
AU  - Li S
AUID- ORCID: 0000-0002-6226-3362
AD  - Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore, Singapore.
FAU - Eaves, Connie J
AU  - Eaves CJ
AUID- ORCID: 0000-0002-3452-1926
AD  - Terry Fox Laboratory, BC Cancer Agency, Vancouver, Canada.
FAU - Goh, Yeow Tee
AU  - Goh YT
AUID- ORCID: 0000-0002-7069-0997
AD  - Department of Haematology, Singapore General Hospital, Singapore, Singapore.
FAU - Cheung, Alice Man Sze
AU  - Cheung AMS
AUID- ORCID: 0000-0003-2195-4017
AD  - Department of Haematology, Singapore General Hospital, Singapore, Singapore.
AD  - Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore, Singapore.
LA  - eng
PT  - Journal Article
DEP - 20230616
PL  - United States
TA  - Sci Adv
JT  - Science advances
JID - 101653440
RN  - 0 (Receptors, Antigen, T-Cell, gamma-delta)
SB  - IM
MH  - Adult
MH  - Humans
MH  - *T-Lymphocytes
MH  - *Epstein-Barr Virus Infections
MH  - Fetal Blood
MH  - Herpesvirus 4, Human
MH  - Receptors, Antigen, T-Cell, gamma-delta/genetics
PMC - PMC10275585
EDAT- 2023/06/16 19:16
MHDA- 2023/06/19 13:08
PMCR- 2023/06/16
CRDT- 2023/06/16 14:03
PHST- 2023/06/19 13:08 [medline]
PHST- 2023/06/16 19:16 [pubmed]
PHST- 2023/06/16 14:03 [entrez]
PHST- 2023/06/16 00:00 [pmc-release]
AID - adf3120 [pii]
AID - 10.1126/sciadv.adf3120 [doi]
PST - ppublish
SO  - Sci Adv. 2023 Jun 16;9(24):eadf3120. doi: 10.1126/sciadv.adf3120. Epub 2023 Jun 
      16.