Immune regulation of cancer

Abstract

Innate and adaptive immune system cells play a major role in regulating the growth of cancer. Although it is commonly thought that an immune response localized to the tumor will inhibit cancer growth, it is clear that some types of inflammation induced in a tumor may also lead to cancer proliferation, invasion, and dissemination. Recent evidence suggests, however, that some patients with cancer can mount an antitumor immune response that has the potential to control or eliminate cancer. Indeed, a so-called "immune response" signature has been described in malignancy that is associated with improved outcomes in several tumor types. Moreover, the presence of specific subsets of T cells, which have the capability to penetrate tumor stroma and infiltrate deep into the parenchyma, identifies patients with an improved prognosis. Immune-based therapies have the potential to modulate the tumor microenvironment by eliciting immune system cells that will initiate acute inflammation that leads to tissue destruction.

Fig 1.

T-helper (Th) 2 and Th1 tumor-specific T cell immunity. (A) Th2 T cells are stimulated by tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs). Together these cells types generate a tumor environment rich in interleukin (IL) -10, IL-4, IL-5, and IL-6. A B-cell response predominates. Regulatory T cells (Tregs) are elicited via these antigen-presenting cells presenting self-antigens, and the resultant secretion of tumor growth factor (TGF) -ß by Treg inhibits the generation of cytotoxic T lymphocytes (CTLs). The result is potential proliferation of tumor cells. (B) Th1 T cells are stimulated by type I dendritic cells (DCs). Together these cell types generate a tumor environment rich in IL-12, interferon (IFN) -γ, tumor necrosis factor (TNF) -α, and IL-2. A CTL response predominates. The result is potential elimination or control of tumor cell growth.

Fig 2.

Elements of imunity-induced tumor rejection. Acute inflammation induced by T-helper (Th) 1, stimulated by dendritic cells (DCs), results in a tumor environment that supports cytotoxic T lymphocytes (CTLs). Cytokines such as interleukin (IL) -12, interferon (IFN) -γ, tumor necrosis factor (TNF) -α, and IL-2 support the proliferation of CTLs, the upregulation of immune receptor molecules on local antigen-presenting cells (APC) and potentially the tumor itself, and the presentation of a variety of tumor-associated antigens such as p53, IFGBP-2, HER2, and hTERT. T cells begin to penetrate through the tumor stroma and kill tumor cells. Gray star shapes represent lysed tumor cells, gray crescent shapes depict dead tumor cells.