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. 2021 Oct 16;19:104. doi: 10.1186/s12964-021-00787-y

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© The Author(s) 2021

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 — The role of EVs post-cancer therapy. A Chemotherapy increases intracellular levels of reactive oxygen species (ROS), which leads to higher EV secretion. EVs derived from tumors that have been exposed to chemotherapeutic drugs have been shown to contain HMG-CoA reductase (HMGCR), which acts in an autocrine/paracrine manner, resulting in a vicious cycle of cholesterol production in cancer cells. Enhanced cholesterol levels can suppress natural immunity through inhibition of NK cells. B Surgical manipulation of tumors may induce circulating tumor cell (CTC) generation while causing an inflammatory state characterized by increased neutrophils in circulation. Tumor-derived EVs in circulation interact with neutrophils to induce NETosis, which allows CTCs to reach target organs. Tumor cells and tumor-derived EVs, along with immune cells, establish a pre-metastatic niche at this site. C After tumor cells have been exposed to ionizing radiation (IR), EV secretion is enhanced with cargo contents involved in AKT signaling, cell motility, DNA damage, and cytokine responses. Under hypoxic conditions, EV secretion is further increased, and these EVs promote migration in tumor cells and angiogenesis