Adoptive Transfer of Anti-Nucleolin T Cells Combined with PD-L1 Inhibition against Triple-Negative Breast Cancer
Issued Date
2022-05-01
Resource Type
ISSN
15357163
eISSN
15388514
Scopus ID
2-s2.0-85129996885
Pubmed ID
35313339
Journal Title
Molecular Cancer Therapeutics
Volume
21
Issue
5
Start Page
727
End Page
739
Rights Holder(s)
SCOPUS
Bibliographic Citation
Molecular Cancer Therapeutics Vol.21 No.5 (2022) , 727-739
Suggested Citation
Thongchot S., Jirapongwattana N., Luangwattananun P., Chiraphapphaiboon W., Chuangchot N., Sa-Nguanraksa D., O-Charoenrat P., Thuwajit P., Yenchitsomanus P.T., Thuwajit C. Adoptive Transfer of Anti-Nucleolin T Cells Combined with PD-L1 Inhibition against Triple-Negative Breast Cancer. Molecular Cancer Therapeutics Vol.21 No.5 (2022) , 727-739. 739. doi:10.1158/1535-7163.MCT-21-0823 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/83746
Title
Adoptive Transfer of Anti-Nucleolin T Cells Combined with PD-L1 Inhibition against Triple-Negative Breast Cancer
Author's Affiliation
Other Contributor(s)
Abstract
Dendritic cell (DC)–based T-cell activation is an alternative immunotherapy in breast cancer. The anti-programmed death ligand 1 (PD-L1) can enhance T-cell function. Nucleolin (NCL) is overexpressed in triple-negative breast cancer (TNBC). The regulation of PD-L1 expression through autophagy and the anti–PD-L1 peptide to help sensitize T cells for NCL-positive TNBC cell killing has not been evaluated. Results showed the worst clinical outcome in patients with high NCL and PD-L1. Self-differentiated myeloid-derived antigen-presenting cells reactive against tumors presenting NCL or SmartDCs-NCL producing GM-CSF and IL-4, could activate NCL-specific T cells. SmartDCs-NCL plus recombinant human ribosomal protein substrate 3 (RPS3) successfully induced maturation and activation of DCs characterized by the reduction of CD14 and the induction of CD11c, CD40, CD80, CD83, CD86, and HLA-DR. Interestingly, SmartDCs-NCL plus RPS3 in combination with anti–PD-L1 peptide revealed significant killing activity of the effector NCL-specific T cells against NCLHigh/ PD-L1High MDA-MB-231 and NCLHigh/PD-L1High HCC70 TNBC cells at the effector: a target ratio of 5:1 in 2-D and 10:1 in the 3-D culture system; and increments of IFNg by the ELISpot assay. No killing effect was revealed in MCF-10A normal mammary cells. Mechanistically, NCL-specific T-cell–mediated TNBC cell killing was through both apoptotic and autophagic pathways. Induction of autophagy by curcumin, an autophagic stimulator, inhibited the expression of PD-L1 and enhanced cytolytic activity of NCL-specific T cells. These findings provide the potential clinical approaches targeting NCLHigh/PD-L1High TNBC cells with NCL-specific T cells in combination with a PD-L1 inhibitor or autophagic stimulator.