Extended Data Fig. 10 ∣. Cancer therapy landscape.
Cancer therapies are grouped into four categories in terms of targets and targeting strategies. Cancer cell-directed therapies aim to directly destruct cancer cells, which include conventional ‘cancer cell therapy’ with targeting approaches such as chemotherapy to eliminate mitotic cancer cells, and ‘cancer cell immunotherapy’ to engage immune effectors such as cytotoxic T lymphocytes (CTLs), killer innate lymphocytes (ILCs) and killer innate-like T cells (ILTCs) to eradicate cancer cells. The cancer immunosurveillance function of CTLs can be revived by immune checkpoint inhibitors such as PD-1 antibodies (anti-PD-1). Cancer environment-directed therapies aspire to rectify the host tissue pathology that fosters tumor growth. A cancer environment hallmark is angiogenesis characterized by a leaky and immature blood vasculature. Conventional ‘cancer environment therapy’ includes anti-angiogenics such as VEGF antibodies (anti-VEGF) that diminish vasculature abundance. Blockade of TGF-β signaling in helper T (Th) cells with 4T-Trap results in enhanced Th2 cell differentiation that promotes vasculature remodeling and tumor tissue healing with cancer cell hypoxia and cancer cell death instigated in avascular regions. 4T-Trap defines a novel modality of ‘cancer environment immunotherapy’.