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From mice to humans: developments in cancer immunoediting
Michele W.L. Teng, … , Wolf-Herman Fridman, Mark J. Smyth
Michele W.L. Teng, … , Wolf-Herman Fridman, Mark J. Smyth
Published August 4, 2015
Citation Information: J Clin Invest. 2015;125(9):3338-3346. https://doi.org/10.1172/JCI80004.
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Review Series

From mice to humans: developments in cancer immunoediting

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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.

Authors

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

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Figure 2

The immune contexture of the tumor microenvironment as a prognostic marker for long-term survival.

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The immune contexture of the tumor microenvironment as a prognostic mark...
(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).

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