Cancer Immunotherapy

Cancer immunotherapy (CIT) is a type of biological therapy, aiming to improve anti-tumor immune responses with fewer off-target effects than chemotherapy. Several types of immunotherapy include: oncolytic virus therapies, cancer vaccines, cytokine therapies, adoptive cell transfer (ACT), and immune checkpoint inhibitors (ICIs). In particular, ICIs and ACT have obtained immense clinical response, but their efficacy varies from person to person. Immune cells can be harnessed to eliminate tumor cells, such as T cells, B cells, NK cells, and myeloid cells. T cells have potent tumor-killing capability, therefore, a plethora of cancer immunotherapy research have focused on inducing T-cell-mediated anti-tumor responses. CTLA-4 and PD-1 are found on the cell surface of T cells as co-inhibitory receptors. The breakthrough in cancer immunotherapy results from the identification and subsequent targeting of checkpoint mechanisms in T cells with monoclonal antibodies against CTLA-4 and programmed death-ligand 1/programmed death-1 (PD-L1/PD-1).

Several types of cancers (e.g., melanoma, mismatch repair-deficient cancers, bladder cancer, and non-small cell lung cancer) have achieved significant clinical responses in T-cell checkpoint blockade therapies. However, single-mode immunotherapy faces challenges such as low immune response, low tumor infiltration, and complex immunosuppressive tumor microenvironment. Recently, combined therapies based on tumor immunity have received extensive attention in the research of enhancing tumor cells immunogenicity and inhibiting their growth. For example, anti CTLA-4 and PD-1, immune checkpoint blockade (ICB) combined with chemotherapy, anti-angiogenic drugs and kinase inhibitors.