TY - JOUR
T1 - CD83 expression characterizes precursor exhausted T cell population
AU - Wu, Zhiwen
AU - Yoshikawa, Toshiaki
AU - Inoue, Satoshi
AU - Ito, Yusuke
AU - Kasuya, Hitomi
AU - Nakashima, Takahiro
AU - Zhang, Haosong
AU - Kotaka, Saki
AU - Hosoda, Waki
AU - Suzuki, Shiro
AU - Kagoya, Yuki
N1 - Funding Information:
This work was supported by the Outstanding Young Immunology Researcher Award (Japanese Society for Immunology and Nippon Becton Dickinson Company); JST FOREST Program (Grant Number JPMJFR2060, Japan); JSPS KAKENHI Grant Number 20H03543 (YK); Aichi Cancer Center Joint Research Project on Priority Areas (YK); the Princess Takamatsunomiya Cancer Research Foundation (YK); Takeda Science Foundation (YK); The Cell Science Research Foundation (YK); Uehara Memorial Foundation (YK and YI); KAKENHI Grant Number 19K09297 (TY), and KAKENHI Grant Number 20K22793 (ZW).
Funding Information:
The authors declare the following competing interests: Y. K. received commercial research grants from Takara Bio and Kyowa Kirin. These financial relationships are unrelated to the present study. Y. K. was provided with flow cytometry antibodies by Nippon Becton Dickinson Company as research support through the Outstanding Young Immunology Researcher Award (hosted by Japanese Society for Immunology and Nippon Becton Dickinson Company). All other authors declare no competing interests.
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - T cell exhaustion is a main obstacle against effective cancer immunotherapy. Exhausted T cells include a subpopulation that maintains proliferative capacity, referred to as precursor exhausted T cells (TPEX). While functionally distinct and important for antitumor immunity, TPEX possess some overlapping phenotypic features with the other T-cell subsets within the heterogeneous tumor-infiltrating T-lymphocytes (TIL). Here we explore surface marker profiles unique to TPEX using the tumor models treated by chimeric antigen receptor (CAR)-engineered T cells. We find that CD83 is predominantly expressed in the CCR7+PD1+ intratumoral CAR-T cells compared with the CCR7-PD1+ (terminally differentiated) and CAR-negative (bystander) T cells. The CD83+CCR7+ CAR-T cells exhibit superior antigen-induced proliferation and IL-2 production compared with the CD83- T cells. Moreover, we confirm selective expression of CD83 in the CCR7+PD1+ T-cell population in primary TIL samples. Our findings identify CD83 as a marker to discriminate TPEX from terminally exhausted and bystander TIL.
AB - T cell exhaustion is a main obstacle against effective cancer immunotherapy. Exhausted T cells include a subpopulation that maintains proliferative capacity, referred to as precursor exhausted T cells (TPEX). While functionally distinct and important for antitumor immunity, TPEX possess some overlapping phenotypic features with the other T-cell subsets within the heterogeneous tumor-infiltrating T-lymphocytes (TIL). Here we explore surface marker profiles unique to TPEX using the tumor models treated by chimeric antigen receptor (CAR)-engineered T cells. We find that CD83 is predominantly expressed in the CCR7+PD1+ intratumoral CAR-T cells compared with the CCR7-PD1+ (terminally differentiated) and CAR-negative (bystander) T cells. The CD83+CCR7+ CAR-T cells exhibit superior antigen-induced proliferation and IL-2 production compared with the CD83- T cells. Moreover, we confirm selective expression of CD83 in the CCR7+PD1+ T-cell population in primary TIL samples. Our findings identify CD83 as a marker to discriminate TPEX from terminally exhausted and bystander TIL.
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U2 - 10.1038/s42003-023-04631-6
DO - 10.1038/s42003-023-04631-6
M3 - Article
C2 - 36906640
AN - SCOPUS:85150218362
SN - 2399-3642
VL - 6
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 258
ER -
