Abstract
The tumor microenvironment (TME) is an integral part of cancer. Recognition of the essential nature of the TME in cancer evolution has led to a shift from a tumor cell-centered view of cancer development to the concept of a complex tumor ecosystem that supports tumor growth and metastatic dissemination. Accordingly, novel targets within the TME have been uncovered that can help direct and improve the actions of various cancer therapies, notably immunotherapies that work by potentiating host antitumor immune responses. Here, we review the composition of the TME, how this attenuates immunosurveillance, and discuss existing and potential strategies aimed at targeting cellular and molecular TME components.
https://academic.oup.com/annonc/article ... 82/2237024
Targeting the tumor microenvironment: removing obstruction to anticancer immune responses and immunotherapy
Re: Targeting the tumor microenvironment: removing obstruction to anticancer immune responses and immunotherapy
the composition of the TME and its interaction with the host immune system
A variety of cell types are found in the TME, which accumulate at different stages of tumor development. Some of the principal cell types to arrive in tumors during their early development are infiltrating inflammatory cells, bone marrow-derived hematopoietic and endothelial progenitor cells, and carcinoma-associated fibroblasts [2]. Early infiltration of tumors by immune cells such as macrophages, lymphocytes, natural killer (NK) cells, and dendritic cells (DCs) is crucial for tumor control [3]. The anticancer immune response generated by these cells is, however, inhibited by the action of immunosuppressive cells, such as myeloid-derived suppressor cell (MDSC) regulatory T cells (Tregs), and type 2-polarized macrophages (M2), which are intrinsically associated with the developing TME (Figure 1) [3, 4]. Cancer cells are able to communicate with other cells and components of the TME through two principal pathways: the first being contact-dependent mechanisms between the particular cancer cell and another cell or with the ECM and the second being contact-independent mechanisms via soluble molecules such as cytokines, lipid mediators, and growth factors. The stromal cells that form a constitutive part of the TME are originally recruited either from the surrounding tissues or from the bone marrow, these making up the cellular components such as endothelial cells, mesenchymal cells, fibroblasts, and myeloid and lymphoid inflammatory cells [1, 5]. Within the TME, stromal cells can become ‘educated’ to become a variety of other cell types that facilitate and sustain cancer cells. This is able to occur due to the phenomenal nature of the TME, which is one of chronic inflammation [6].
A variety of cell types are found in the TME, which accumulate at different stages of tumor development. Some of the principal cell types to arrive in tumors during their early development are infiltrating inflammatory cells, bone marrow-derived hematopoietic and endothelial progenitor cells, and carcinoma-associated fibroblasts [2]. Early infiltration of tumors by immune cells such as macrophages, lymphocytes, natural killer (NK) cells, and dendritic cells (DCs) is crucial for tumor control [3]. The anticancer immune response generated by these cells is, however, inhibited by the action of immunosuppressive cells, such as myeloid-derived suppressor cell (MDSC) regulatory T cells (Tregs), and type 2-polarized macrophages (M2), which are intrinsically associated with the developing TME (Figure 1) [3, 4]. Cancer cells are able to communicate with other cells and components of the TME through two principal pathways: the first being contact-dependent mechanisms between the particular cancer cell and another cell or with the ECM and the second being contact-independent mechanisms via soluble molecules such as cytokines, lipid mediators, and growth factors. The stromal cells that form a constitutive part of the TME are originally recruited either from the surrounding tissues or from the bone marrow, these making up the cellular components such as endothelial cells, mesenchymal cells, fibroblasts, and myeloid and lymphoid inflammatory cells [1, 5]. Within the TME, stromal cells can become ‘educated’ to become a variety of other cell types that facilitate and sustain cancer cells. This is able to occur due to the phenomenal nature of the TME, which is one of chronic inflammation [6].
Debbie
Re: Targeting the tumor microenvironment: removing obstruction to anticancer immune responses and immunotherapy
Good guys versus bad guys in the tumor microenvironment: a balance. The balance between a large number of different immune cells, immune factors, and signaling molecules determines the outcome of the antitumor immune response. CTL, cytotoxic T lymphocyte; Th, T helper; pTh17, pathogenic T helper 17; NK, natural killer; DC, dendritic cell; IFN, interferon; IL, interleukin; GM-CSF, granulocyte macrophage colony-stimulating factor; TGF, transforming growth factor; IDO, indole 2,3-dioxygenase; PGE, prostaglandin E; MDSC, myeloid-derived suppressor cell; TAM, tumor-associated macrophage.
Debbie