J Cancer 2021; 12(22):6629-6639. doi:10.7150/jca.62123 This issue Cite

Research Paper

Synergistic killing effects of PD-L1-CAR T cells and colorectal cancer stem cell-dendritic cell vaccine-sensitized T cells in ALDH1-positive colorectal cancer stem cells

Liu Liu1*, Yuanyuan Liu1*, Yang Xia2*, Guanlong Wang1, Xiushan Zhang1, Huan Zhang3, Yang Xu1, Yuan Yuan1, Shangquan Liu1, Yi Wang1✉

1. The First People's Hospital of Hefei/The Third Affiliated Hospital of Anhui Medical University, Hefei 230061, P.R. China.
2. Taizhou People's Hospital/The Fifth Affiliated Hospital of Nantong University, Taizhou 225300, P.R. China.
3. Linquan County People's Hospital, Linquan 236400, P.R. China.
*These authors contribute equally to this work.

Citation:
Liu L, Liu Y, Xia Y, Wang G, Zhang X, Zhang H, Xu Y, Yuan Y, Liu S, Wang Y. Synergistic killing effects of PD-L1-CAR T cells and colorectal cancer stem cell-dendritic cell vaccine-sensitized T cells in ALDH1-positive colorectal cancer stem cells. J Cancer 2021; 12(22):6629-6639. doi:10.7150/jca.62123. https://www.jcancer.org/v12p6629.htm
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Abstract

Graphic abstract

Cancer stem cells (CSCs) are characterized by self-renewal and unlimited proliferation, providing a basis for tumor occurrence, metastasis, and recurrence. Because CSCs are highly resistant to conventional chemotherapy and radiotherapy, various immunotherapies, particularly chimeric antigen receptor T cell (CAR-T) therapy and dendritic cell (DC)-based vaccine therapy, are currently being developed. Accordingly, in this study, we evaluated programmed cell death ligand-1 (PD-L1) expression in colorectal CSCs (CCSCs) and non-CCSCs and designed a combination immunotherapy synchronously utilizing PD-L1-CAR-T cells together with CCSC-DC vaccine-sensitized T cells for the treatment of colorectal cancer. PD-L1-CAR-T cells specifically recognized the PD-L1 molecule on CCSCs by binding to the extracellular domain of programmed cell death-1. The CCSC-DC vaccine was prepared using CCSC lysates. We found that aldehyde dehydrogenase 1 (ALDH1)-positive CCSCs were abundant in samples from patient tumor tissues and cancer cell lines. Moreover, PD-L1 was highly expressed in ALDH1-positive CCSCs compared with that in non-CCSCs. Monotherapy with PD-L1-CAR-T cells or CCSC-DC vaccine only elicited moderate tumor remission both in vitro and in vivo. However, combination therapy markedly killed cancer cells and relieved the tumor burden in mice. Our findings may provide a novel strategy for the clinical treatment of colorectal malignancy.

Keywords: colorectal cancer stem cells, PD-L1-CAR T cells, colorectal cancer stem cell-dendritic cell vaccine, synergistic killing, ALDH1


Citation styles

APA
Liu, L., Liu, Y., Xia, Y., Wang, G., Zhang, X., Zhang, H., Xu, Y., Yuan, Y., Liu, S., Wang, Y. (2021). Synergistic killing effects of PD-L1-CAR T cells and colorectal cancer stem cell-dendritic cell vaccine-sensitized T cells in ALDH1-positive colorectal cancer stem cells. Journal of Cancer, 12(22), 6629-6639. https://doi.org/10.7150/jca.62123.

ACS
Liu, L.; Liu, Y.; Xia, Y.; Wang, G.; Zhang, X.; Zhang, H.; Xu, Y.; Yuan, Y.; Liu, S.; Wang, Y. Synergistic killing effects of PD-L1-CAR T cells and colorectal cancer stem cell-dendritic cell vaccine-sensitized T cells in ALDH1-positive colorectal cancer stem cells. J. Cancer 2021, 12 (22), 6629-6639. DOI: 10.7150/jca.62123.

NLM
Liu L, Liu Y, Xia Y, Wang G, Zhang X, Zhang H, Xu Y, Yuan Y, Liu S, Wang Y. Synergistic killing effects of PD-L1-CAR T cells and colorectal cancer stem cell-dendritic cell vaccine-sensitized T cells in ALDH1-positive colorectal cancer stem cells. J Cancer 2021; 12(22):6629-6639. doi:10.7150/jca.62123. https://www.jcancer.org/v12p6629.htm

CSE
Liu L, Liu Y, Xia Y, Wang G, Zhang X, Zhang H, Xu Y, Yuan Y, Liu S, Wang Y. 2021. Synergistic killing effects of PD-L1-CAR T cells and colorectal cancer stem cell-dendritic cell vaccine-sensitized T cells in ALDH1-positive colorectal cancer stem cells. J Cancer. 12(22):6629-6639.

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