[Phenotypic and functional changes in endogenous T cells during the bystander effect in different disease states of lymphomas treated with CD19-targeted chimeric antigen receptor T cells].
- 1Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China Institute of Hematology, Xuzhou Medical University, Xuzhou 221002, China.
- 2Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China.
- 3Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China Institute of Hematology, Xuzhou Medical University, Xuzhou 221002, China Huaihai Medical Science and Technology Innovation and Public Service Center, Xuzhou 221005, China.
Abstract
Objective: To investigate the bystander effect of endogenous T cells within the tumor microenvironment, as well as their roles and phenotypic changes during remission and relapse in mice with B-cell lymphoma receiving CD19-targeted chimeric antigen receptor T (CAR-T) cell therapy. Methods: At the Institute of Hematology, Xuzhou Medical University, in vitro experiments and mouse models were established using BALB/c mice to evaluate the efficacy of CD19 CAR-T cells in treating CD19(-) and CD19(+)A20 lymphomas. In the in vitro experiments, the mice were categorized into the following groups based on the type of co-cultured cells: activated T cell (n=3) and CD19-targeted CAR-T cell (n=3) groups. In the CD19(-) A20 lymphoma mouse model, the mice were assigned to the activated T-cell (n=5) and CD19 CAR-T cell treatment (n=5) groups based on the type of cells used for treatment. For the CD19(+) A20 lymphoma mouse model, the mice were divided into the activated T cell treatment (n=3-8), CD19 CAR-T cell treatment (n=14), remission (clinical score ≤ 1), and relapse (clinical score >1) groups. Therapeutic efficacy was evaluated, and flow cytometry was used to analyze the subsets, activation status, and cytokine secretion profiles of endogenous T cells at different disease states. Results: In vitro experiments demonstrated that, compared with the activated T-cell group, CD19 CAR-T cells exerted no specific cytotoxic effect on CD19(-) A20 cells [survival rates: (40.83±1.70) %vs (39.07±1.40) %, P=0.238]. However, in immunocompetent mice, compared with the activated T-cell treatment, CD19-targeted CAR-T cell therapy resulted in reduced weight [ (0.14±0.10) vs (0.81±0.24) g, P=0.002] and significantly diminished subcutaneous CD19(-) A20 tumor volume [ (335.40±130.20) vs (542.00±302.40) mm(3), P=0.004], accompanied by increased infiltration of endogenous CD3(+) T cells [ (36.34±6.53) % vs (9.49±9.42) %, P=0.001]. CD8(+) T cells exhibited increased CD69 expression [ (21.38±4.85) % vs (3.15±1.16) %, P=0.001] and a trend toward decreased expression of exhaustion-associated molecules PD-1 and TIGIT (all P value >0.05). In the mouse model of CD19(+) A20 lymphoma remission and relapse, upon disease relapse, the proportion of endogenous CD8(+) T cells in the spleen (SP) and bone marrow (BM) showed a downward trend during disease relapse compared with that during the remission period, the CD69 expression intensity decreased (CD4(+) T cell: BM: 733.20±274.40 vs 1 093.00±131.20, P=0.013; SP: 290.50±142.40 vs 478.70±63.94, P=0.018; CD8(+) T cell: BM: 1 223.00±391.50 vs 1 892.00±540.40, P=0.041; SP: 342.30±258.10 vs 500.00±113.90, P=0.325) and the secretion levels of cytokines IFN-γ, TNF-α, GM-CSF, and granzyme B were all diminished (all P value <0.05). During relapse, the proportion of effector T cell (Teff) cells decreased significantly, whereas the proportions of naive T cell (Tn) cells and memory T cell (Tm) cells increased significantly (all P value <0.05) . Conclusion: The specific cytotoxic activity of CD19-targeted CAR-T cells in vivo can activate endogenous T cells and induce a bystander effect, which non-specifically inhibits lymphoma growth. However, following disease relapse, the cytotoxic function of endogenous T cells gradually diminishes and shifts toward resting and memory phenotypes.
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BibTeX
@article{yan2026phenotypic,
title = {{[Phenotypic and functional changes in endogenous T cells during the bystander effect in different disease states of lymphomas treated with CD19-targeted chimeric antigen receptor T cells].}},
author = {F Yan and D H Tang and W W Li and Y Gu and C X Ren and W Sang and K Zhao},
journal = {Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi},
year = {2026},
month = aug,
doi = {10.3760/cma.j.cn121090-20260129-00066},
url = {https://europepmc.org/article/MED/42851179},
note = {CC BY},
}
RIS
TY - JOUR
TI - [Phenotypic and functional changes in endogenous T cells during the bystander effect in different disease states of lymphomas treated with CD19-targeted chimeric antigen receptor T cells].
AU - F Yan
AU - D H Tang
AU - W W Li
AU - Y Gu
AU - C X Ren
AU - W Sang
AU - K Zhao
PY - 2026
DA - 2026/08/01
JO - Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi
DO - 10.3760/cma.j.cn121090-20260129-00066
UR - https://europepmc.org/article/MED/42851179
AB - Objective: To investigate the bystander effect of endogenous T cells within the tumor microenvironment, as well as their roles and phenotypic changes during remission and relapse in mice with B-cell lymphoma receiving CD19-targeted chimeric antigen receptor T (CAR-T) cell therapy. Methods: At the Institute of Hematology, Xuzhou Medical University, in vitro experiments and mouse models were established using BALB/c mice to evaluate the efficacy of CD19 CAR-T cells in treating CD19(-) and CD19(+)A20 lymphomas. In the in vitro experiments, the mice were categorized into the following groups based on the type of co-cultured cells: activated T cell (n=3) and CD19-targeted CAR-T cell (n=3) groups. In the CD19(-) A20 lymphoma mouse model, the mice were assigned to the activated T-cell (n=5) and CD19 CAR-T cell treatment (n=5) groups based on the type of cells used for treatment. For the CD19(+) A20 lymphoma mouse model, the mice were divided into the activated T cell treatment (n=3-8), CD19 CAR-T cell treatment (n=14), remission (clinical score ≤ 1), and relapse (clinical score >1) groups. Therapeutic efficacy was evaluated, and flow cytometry was used to analyze the subsets, activation status, and cytokine secretion profiles of endogenous T cells at different disease states. Results: In vitro experiments demonstrated that, compared with the activated T-cell group, CD19 CAR-T cells exerted no specific cytotoxic effect on CD19(-) A20 cells [survival rates: (40.83±1.70) %vs (39.07±1.40) %, P=0.238]. However, in immunocompetent mice, compared with the activated T-cell treatment, CD19-targeted CAR-T cell therapy resulted in reduced weight [ (0.14±0.10) vs (0.81±0.24) g, P=0.002] and significantly diminished subcutaneous CD19(-) A20 tumor volume [ (335.40±130.20) vs (542.00±302.40) mm(3), P=0.004], accompanied by increased infiltration of endogenous CD3(+) T cells [ (36.34±6.53) % vs (9.49±9.42) %, P=0.001]. CD8(+) T cells exhibited increased CD69 expression [ (21.38±4.85) % vs (3.15±1.16) %, P=0.001] and a trend toward decreased expression of exhaustion-associated molecules PD-1 and TIGIT (all P value >0.05). In the mouse model of CD19(+) A20 lymphoma remission and relapse, upon disease relapse, the proportion of endogenous CD8(+) T cells in the spleen (SP) and bone marrow (BM) showed a downward trend during disease relapse compared with that during the remission period, the CD69 expression intensity decreased (CD4(+) T cell: BM: 733.20±274.40 vs 1 093.00±131.20, P=0.013; SP: 290.50±142.40 vs 478.70±63.94, P=0.018; CD8(+) T cell: BM: 1 223.00±391.50 vs 1 892.00±540.40, P=0.041; SP: 342.30±258.10 vs 500.00±113.90, P=0.325) and the secretion levels of cytokines IFN-γ, TNF-α, GM-CSF, and granzyme B were all diminished (all P value <0.05). During relapse, the proportion of effector T cell (Teff) cells decreased significantly, whereas the proportions of naive T cell (Tn) cells and memory T cell (Tm) cells increased significantly (all P value <0.05) . Conclusion: The specific cytotoxic activity of CD19-targeted CAR-T cells in vivo can activate endogenous T cells and induce a bystander effect, which non-specifically inhibits lymphoma growth. However, following disease relapse, the cytotoxic function of endogenous T cells gradually diminishes and shifts toward resting and memory phenotypes.
SN - 0253-2727
SN - 2707-9740
ER -