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. 2021 Apr 6;14:55. doi: 10.1186/s13045-021-01053-x

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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. 2 — Effects of TGF-β on Antitumor Immunity. TGF-β is produced by multiple cell types within the TME. TGF-β can increase (black arrow) or decrease (red block) the proliferation and functional activity of immune effectors with tumor-promoting or tumor-suppressive outcomes. TGF-β enhances pro-inflammatory Th17 cells along with IL-6. TGF-β also blocks the IFN-γ-mediated induction of pro-inflammatory Th1 cells as well as the IL-4-dependent production of Th2 cells to decrease tumor suppression. TGF-β induces naïve T cell differentiation into Tregs and Treg expansion with IL-2. Tregs then reduce CD8⁺ T cell development and expansion to increase immune suppression. TGF-β also reduces the production of mast cells (to reduce superoxide and NO production), natural killer (NK) cells (reduced cytokine and IFN-γ production), B cells (reduced IgA secretion), polymorphonuclear cells (PMNs, reduced degranulation), M1 macrophages (reduced pro-inflammatory cytokines, e.g., IL-12) and reduced dendritic cells (DCs) leading to reduced antigen presentation and cytokine production. TGF-β promotes the differentiation and expansion of MDSCs as well as the production of M2 macrophages leading to increased anti-inflammatory cytokines IL-4 and IL-10