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Review
. 2015 Sep;125(9):3338-46.
doi: 10.1172/JCI80004. Epub 2015 Aug 4.

From mice to humans: developments in cancer immunoediting

Michele W L Teng, Jerome Galon, Wolf-Herman Fridman, Mark J Smyth
Review

From mice to humans: developments in cancer immunoediting

Michele W L Teng et al. J Clin Invest. 2015 Sep.

Abstract

Cancer immunoediting explains the dual role by which the immune system can both suppress and/or promote tumor growth. Although cancer immunoediting was first demonstrated using mouse models of cancer, strong evidence that it occurs in human cancers is now accumulating. In particular, the importance of CD8+ T cells in cancer immunoediting has been shown, and more broadly in those tumors with an adaptive immune resistance phenotype. This Review describes the characteristics of the adaptive immune resistance tumor microenvironment and discusses data obtained in mouse and human settings. The role of other immune cells and factors influencing the effector function of tumor-specific CD8+ T cells is covered. We also discuss the temporal occurrence of cancer immunoediting in metastases and whether it differs from immunoediting in the primary tumor of origin.

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Figures

Figure 2
Figure 2. The immune contexture of the tumor microenvironment as a prognostic marker for long-term survival.
(A) Cellular components of the tumor stroma include blood and lymphatic vessels, infiltrating and resident leukocytes, various populations of fibroblasts, and mesenchymal support cells unique to each tissue environment. The immune contexture is defined as the type, density, functional orientation, and location of immune cells within distinct tumor regions. A spectrum of soluble cytokines and chemokines regulate the entry of immune cells into tumors, which then have different effects on tumor progression. All types of immune cells are present in the tumor, including macrophages, DCs, mast cells, NK cells, naive and memory lymphocytes, B cells, and effector T cells (including various subsets of T cells: Th cells, Th1, Th2, Th17, Tregs, Tfh, and CTLs). Immune cells can be located in the core of the tumor, in the invasive margin, or in the adjacent TLSs. Few CD8+ T cells are seen in human TLSs, which are similar to secondary follicles in lymph nodes. TLSs contain naive and memory T cells, Tfh cells, B cells, and mature DCs. FDC, follicular DC. (B) High expression levels of various immune parameters that define a Th1 immune contexture, as well as the presence of Tfh cells, B cells, CXCL13, IL-21, and IL-15, are associated with prolonged DFS and/or improved OS in CRC (figures adapted from refs. 16, 23).
Figure 1
Figure 1. Major mechanisms of tumor escape and therapeutic options.
The mechanisms of tumor cell escape can be classified into three major categories: (A) reduced immune recognition and immune cell stimulation through downregulation or loss of strong tumor antigens and antigen-presenting machinery or lack of costimulatory molecules; (B) upregulation of resistance mechanisms against the cytotoxic effectors of immunity (e.g., STAT3) or increased expression of prosurvival or growth factor genes (e.g., Bcl-2, Her2/neu); and (C) establishment of an immunosuppressive tumor microenvironment via (a) production of cytokines (e.g., VEGF, TGF-β) and metabolic factors (e.g., adenosine, PGE2); (b) induction and/or recruitment of Tregs and MDSCs; or (c) induction of adaptive immune resistance through ligation of inhibitory receptors (e.g., CTLA-4, PD-1, Tim-3) on immune effector cells. Over the past two decades, strategies to target these pathways have been the subject of intense investigation, and some of these are listed in the figure. iNOS, inducible NOS.
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References

    1. Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science. 2011;331(6024):1565–1570. doi: 10.1126/science.1203486. - DOI - PubMed
    1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–674. doi: 10.1016/j.cell.2011.02.013. - DOI - PubMed
    1. Dunn GP, Old LJ, Schreiber RD. The immunobiology of cancer immunosurveillance and immunoediting. Immunity. 2004;21(2):137–148. doi: 10.1016/j.immuni.2004.07.017. - DOI - PubMed
    1. Diamond MS, et al. Type I interferon is selectively required by dendritic cells for immune rejection of tumors. J Exp Med. 2011;208(10):1989–2003. doi: 10.1084/jem.20101158. - DOI - PMC - PubMed
    1. Vesely MD, Kershaw MH, Schreiber RD, Smyth MJ. Natural innate and adaptive immunity to cancer. Annu Rev Immunol. 2011;29:235–271. doi: 10.1146/annurev-immunol-031210-101324. - DOI - PubMed

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