Natural products and their derivatives as immune check point inhibitors: Targeting cytokine/chemokine signalling in cancer.

Cancer immunotherapy is the new generation and widely accepted form of tumour treatment. It is, however, associated with exclusive challenges which include organ-specific inflammation, and single-target strategies. Therefore, approaches that can enhance the efficiency of existing immunotherapies and expand their indications are required for the further development of immunotherapy. Natural products and medicines are stated to have this desired effect on cancer immunotherapy (adoptive immune-cells therapy, cancer vaccines, and immune-check point inhibitors). They refurbish the immunosuppressed tumour microenvironment, which is the primary location of interaction of tumour cells with the host immune system. Various immune cell subsets, via interaction with cytokine/chemokine receptors, are recruited into this microenvironment, and these subsets have roles in tumour progression and treatment responsiveness. This review summarises cytokine/chemokine signalling, types of cancer immunotherapy and the herbal medicine-derived natural products targeting cytokine/chemokines and immune checkpoints. These natural compounds possess immunomodulatory activities and exert their anti-tumour effect by either blocking the interaction or modulating the expression of the proteins linked with immune checkpoint signaling pathways. Some compounds also show a synergistic effect in combination with existing monoclonal antibody drugs to reverse the tumour microenvironment. Additionally, we have also reported some studies about the derivatives and formulations used to overcome the limitations of natural forms. This review can provide important insights for directing future research.