TGF-ß suppresses type 2 immunity to cancer.

ABSTRACT

The immune system uses two distinct defence strategies against infections microbe-directed pathogen destruction characterized by type 1 immunity1, and host-directed pathogen containment exemplified by type 2 immunity in induction of tissue repair2. Similar to infectious diseases, cancer progresses with self-propagating cancer cells inflicting host-tissue damage. The immunological mechanisms of cancer cell destruction are well defined3-5, but whether immune-mediated cancer cell containment can be induced remains poorly understood. Here we show that depletion of transforming growth factor-ß receptor 2 (TGFBR2) in CD4+ T cells, but not CD8+ T cells, halts cancer progression as a result of tissue healing and remodelling of the blood vasculature, causing cancer cell hypoxia and death in distant avascular regions. Notably, the host-directed protective response is dependent on the T helper 2 cytokine interleukin-4 (IL-4), but not the T helper 1 cytokine interferon-γ (IFN-γ). Thus, type 2 immunity can be mobilized as an effective tissue-level defence mechanism against cancer.