American Association for Cancer Research
10780432ccr160040-sup-160567_2_supp_3537818_n8n23t.png (2.87 MB)

Supplemental Figure 5 from CTLA-4 Limits Anti-CD20–Mediated Tumor Regression

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posted on 2023-03-31, 20:10 authored by Zhenhua Ren, Jingya Guo, Jing Liao, Yan Luan, Zhida Liu, Zhichen Sun, Xiaojuan Liu, Yong Liang, Hua Peng, Yang-Xin Fu

Supplementary Figure 5. FTY720 could efficiently prohibit lymphocytes from exiting the lymphoid organ.


National Nature and Science Foundation

National Science and Technology

National Nature Science Foundation

Ministry of Science and Technology

National Cancer Institute



Purpose: The inhibition of tumor growth by anti-CD20 antibody (Ab) treatment is mediated by Ab- and complement-dependent cytotoxicity in xenograft tumor models. In addition, anti-CD20 therapy for B-cell lymphoma can result in intrinsic and extrinsic tumor resistance to further Ab treatment. However, adaptive immune response–related resistance has not been well studied in anti-CD20–mediated tumor control, and adaptive immunity has long been underestimated. The purpose of this study was to explore whether T cells are involved in mediating the effects of anti-CD20 therapy and what factors contribute to adaptive immune response–related resistance.Experimental Design: Using a syngeneic mouse B-cell lymphoma model, we investigated the role of CD8+ T cells in anti-CD20–mediated tumor regression. Furthermore, we revealed how the tumor-specific T-cell response was initiated by anti-CD20. Finally, we studied adaptive immune response–related resistance in advanced B-cell lymphoma.Results: CD8+ T cells played an essential role in anti-CD20–mediated tumor regression. Mechanistically, anti-CD20 therapy promoted dendritic cell (DC)-mediated cross-presentation. Importantly, macrophages were also necessary for the increase in the tumor-specific CTL response after anti-CD20 treatment, via the production of type I IFN to activate DC function. Furthermore, adaptive resistance is gradually developed through the CTLA-4 pathway in Treg cells in larger lymphomas. Further blockade of CTLA-4 can synergize with anti-CD20 treatment in antitumor activities.Conclusions: The therapeutic function of anti-CD20 depends on tumor-specific CD8+ T-cell responses initiated by anti-CD20 through macrophages and DCs. CTLA-4 blockade can synergize with anti-CD20 to overcome adaptive immune response–related resistance in advanced B-cell lymphoma. Clin Cancer Res; 23(1); 193–203. ©2016 AACR.

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