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. 2022 Oct 25;15:153. doi: 10.1186/s13045-022-01364-7

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© The Author(s) 2022

Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 1 — Current immune checkpoint receptors and their respective ligands. Many immune checkpoints expressed on the surface of T cells, such as PD-1, CTLA-4, LAG-3, TIGIT, VISTA, and TIM-3, bind to their respective ligands on APCs and/or tumor cells, eliciting positive and/or negative activity in the T cell response. TIM-3 also participates in associated signaling through PtdSer, HMGB-1 and Gal-9 in dying tumor cells. Notably, checkpoints such as PD-L1, CD80, CD226, and VISTA (B7-H5) are expressed on both T cells and APC/tumor cells. B7-H3 is also expressed on the surface of both T cells and APC/tumor cells, but its receptors have not been clearly elucidated, which has engendered great enthusiasm in cancer immunology investigators. In this article, we identify TLT-2, IL20RA, and PLA2R1 as three potential receptors for B7-H3. “+” in green indicates the immunostimulatory (positive) signal, and “−” in red indicates the immunosuppressive (negative) signal. PtdSer, phosphatidylserine; HMGB-1, high-mobility group protein B1; Gal-9, galectin-9