Fig. 5

Combination therapy of immune checkpoint inhibitors with conventional therapies may enhance antitumor responses. Molecularly targeted therapies attack cells with specific genetic characteristics resulting in the release of multiple tumor neoantigens. Tumor neoantigens are taken up by antigen presenting cells that then present them in the context of B7 costimulatory molecules and major histocompatibility complex to T cells. T cells are partially activated but overexpress checkpoint molecules, such as CTLA-4 and PD1, which prevent them from becoming fully activated at the tumor site. Immune checkpoint blockade unleashes pre-existing anticancer T cell responses and licenses T cells to attack the cancer cells. CTLA-4, Cytotoxic T lymphocyte-associated protein 4; MCH, Major histocompatibility complex; PD1, Programmed cell death protein 1; PD-L1, PD1 ligand; TCR, T cell receptor. (Adapted from [4])