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Review
. 2018 Oct 1;32(19-20):1267-1284.
doi: 10.1101/gad.314617.118.

Roles of the immune system in cancer: from tumor initiation to metastatic progression

Hugo Gonzalez  1 , Catharina Hagerling  1 , Zena Werb  1
Affiliations
Review

Roles of the immune system in cancer: from tumor initiation to metastatic progression

Hugo Gonzalez et al. Genes Dev. .

Abstract

The presence of inflammatory immune cells in human tumors raises a fundamental question in oncology: How do cancer cells avoid the destruction by immune attack? In principle, tumor development can be controlled by cytotoxic innate and adaptive immune cells; however, as the tumor develops from neoplastic tissue to clinically detectable tumors, cancer cells evolve different mechanisms that mimic peripheral immune tolerance in order to avoid tumoricidal attack. Here, we provide an update of recent accomplishments, unifying concepts, and future challenges to study tumor-associated immune cells, with an emphasis on metastatic carcinomas.

Keywords: cancer heterogeneity; disseminated tumor cells; immune cross-talk; metastasis-associated immune cells; patient-derived xenograft; tumor-associated macrophages.

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Figures

Figure 1.
Figure 1.
Chronic inflammation is a necessary consequence of cancer progression. Different inflammatory conditions can lead to neoplastic transformation. However, whether or not the inflammation is present in the origin of carcinogenesis, most tumors progress to a state of chronic inflammation that fuels different aspects of tumor progression, including genomic and epigenomic instability, immune evasion, angiogenesis, and metastatic dissemination.
Figure 2.
Figure 2.
The balance between effector and tolerogenic immune response dictates tumor fate. During the early stages of tumor development, effector immune cells eliminate immunogenic cancer cells. Selected cancer cells that survive progress to clinically detectable tumors adopt different strategies of peripheral immune tolerance and recruitment of immunosuppressive immune cells that can subdue other tumoricidal cells. For abbreviations and further details, see the text.
Figure 3.
Figure 3.
Roles of innate immune cells in metastatic cancers. An overview of the protumor and anti-tumor roles of innate immune cells in cancer, indicating the specific functions and the outcomes. Processes such as angiogenesis, ECM remodeling, and immune evasion are mediated by TAMs, tumor-associated neutrophils (TANs), and immature dendritic cells (DCs), resulting in rapid tumor progression and metastasis. In contrast, the recruitment of cytotoxic macrophages and neutrophils, NK cells, and mature DCs results in elimination of tumor cells in primary sites and after dissemination. (DTC) Disseminated tumor cell. For other abbreviations and further details, see the text.
Figure 4.
Figure 4.
Dual role of T cells in cancer and metastasis. During the early stages of tumorigenesis, the T-cell response against tumor-derived antigens controls tumor progression, characterized by secretion of Th-1 cytokines (IFN-γ, IL-2, and IL-12), NK cell recruitment, and the presence of CTLs. As a consequence of the constant selective pressure of the effector response, tumor variants are selected and escape immune recognition. These tumor cells enter a phase of outgrowth that is not blocked by effector immune cells. Concomitantly, the tumor induces the recruitment of regulatory CD4+ T cells (Tregs) that counteract anti-tumor immune cells by diverse mechanisms. Tumors with high infiltration of Tregs are associated with the worst prognosis. For abbreviations and further details, see the text.
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