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. 2023 Jan 30;22:20. doi: 10.1186/s12943-023-01723-z

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© The Author(s) 2023

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. 3 — Possible combination therapies for CAR-NK cells. A Combination of CAR-NK cells with chemotherapy: The upregulation of tumor associated antigen (TAA) on cancer cells (a) enhances CAR-NK cells interaction with cancer cells and promotes their cytotoxic activity. Moreover, by decreasing Treg and MDSCs, chemotherapy (b) promotes CAR-NK cells proliferation, infiltration and prolongates their survival in the TME. Therefore, combination of CAR-NK cells with chemotherapy would (c) enhance tumor cell death. B Combination of CAR-NK cells with oncolytic viruses: The tumor debulking induced by oncolytic viruses (a) enhances CAR-NK cells infiltration, proliferation, and activation and (b) proinflammatory cytokines production. Chemotherapy can (c) deliver a universal tumor cell marker to be targeted by CAR-NK cells. Combination of CAR-NK cells with oncolytic viruses will (d) induce double killing of tumor cells by the virus and the CAR-NK cells