1. Academic Validation
  2. CXCL9 secreted by tumor-associated dendritic cells up-regulates PD-L1 expression in bladder cancer cells by activating the CXCR3 signaling

CXCL9 secreted by tumor-associated dendritic cells up-regulates PD-L1 expression in bladder cancer cells by activating the CXCR3 signaling

  • BMC Immunol. 2021 Jan 6;22(1):3. doi: 10.1186/s12865-020-00396-3.
Weigang Xiu 1 2 3 Jingjing Luo 4 5
Affiliations

Affiliations

  • 1 Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, 610041, PR China.
  • 2 Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, 610041, PR China.
  • 3 Department of Thoracic Oncology and State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, PR China.
  • 4 Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, 610041, PR China. [email protected].
  • 5 Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, 610041, PR China. [email protected].
Abstract

Background: Tumor-associated dendritic cells (TADCs) can interact with tumor cells to suppress anti-tumor T cell immunity. However, there is no information on whether and how TADCs can modulate programmed death-ligand 1 (PD-L1) expression by Cancer cells.

Methods: Human peripheral blood monocytes were induced for DCs and immature DCs were cultured alone, or co-cultured with bladder Cancer T24 or control SV-HUC-1 cells, followed by stimulating with LPS for DC activation. The activation status of DCs was characterized by flow cytometry and allogenic T cell proliferation. The levels of chemokines in the supernatants of co-cultured DCs were measured by CBA-based flow cytometry. The impacts of CXCL9 on PD-L1, STAT3 and Akt expression and STAT3 and Akt phosphorylation in T24 cells were determined by flow cytometry and Western blot.

Results: Compared with the control DCs, TADCs exhibited immature phenotype and had significantly lower capacity to stimulate allogenic T cell proliferation, particularly in the presence of recombinant CXCL9. TADCs produced significantly higher levels of CXCL9, which enhanced PD-L1 expression in T24 cells. Pre-treatment with AMG487 abrogated the CXCL9-increased PD-L1 expression in T24 cells. Treatment with CXCL9 significantly enhanced STAT3 and Akt activation in T24 cells.

Conclusions: TADCs produced high levels of CXCL9 that increased PD-L1 expression in bladder Cancer T24 cells by activating the CXCR3-related signaling. Our findings may shed new lights in understanding the regulatory roles of TADCs in inhibiting antitumor T cell responses and promoting tumor growth.

Keywords

Bladder cancer; CXCL9/CXCR3; Programmed death-ligand 1; STAT3/AKT; Tumor-associated dendritic cells.

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