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. 2021 Jul 21;36(1):138–154. doi: 10.1038/s41375-021-01301-6

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 6 — HLA-A2-specific XBP1/CD138/CS1-specific CTL (N = 5) were generated by four cycles of weekly stimulation of CD3⁺ T cells with immunogenic XBP1/CD138/CS1 peptides and then examined for their phenotypic profile and functional activities against MM. A Upon fourth cycle of peptides stimulation, time-dependent T-cell activation (CD69) and checkpoint (CTLA4, PD1, LAG3, VISTA, TIM3) upregulation were detected on MM-specific CTL. B, C Immune checkpoint treatment enhanced (anti-LAG3 > anti-PD1) the poly-functional activities of antigen-specific T cells in response to HLA-A2-matched U266 MM cells. B Induced proliferation of total CD8⁺ CTL as well as central memory, effector memory, CD28⁺ and CD38⁺ CTL subsets. C Increased CD107a⁺ degranulation and IFN-γ production associated with a higher CD8⁺ CTL proliferation.