Since cancer cells have adapted to modify important signalling pathways for increased cellular growth, tumour progression, and angiogenesis, these molecular and cellular alterations represent attractive targets for comprehensive cancer treatment strategies. In this context, crucial elements in pertinent signalling pathways for malignant cells and/or immune cells, including EGFR/KRAS, PI3K-AKT/mTOR, JAK/STAT, p53, PD-1/PD-L1, and epigenetic or immunological pathways, are currently the subject of research . Furthermore, one of the most promising methods for eliciting therapeutic anticancer immunity is immune checkpoint blockage. Immune checkpoint pathways govern and eliminate infections, cancer, and resistance to a variety of autoantigens. Since ligand-receptor interactions trigger a number of immunological checkpoints, antibodies can readily block them or recombinant forms of ligands or receptors can regulate them. The first immunotherapeutics approved by the US Food and Drug Administration (FDA) were antibodies directed against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4). Early clinical results using immune checkpoint protein inhibitors, such as programmed cell death protein 1 (PD-1), suggest a number of chances to boost antitumor immunity with the goal of producing long-term clinical effects.  In addition to classic checkpoint blockade, new therapy methods that target these signaling pathways have emerged and are being investigated in preclinical animals, offering new avenues for the discovery of next-generation immunotherapies.

This Special Issue presents important insights into the efficacy and methods of immune checkpoint control by oncogenic signalling pathways that may represent potential therapeutic targets, as well as the function of the tumour microenvironment. We also encourage submissions for publication consideration in this issue that address the role of natural products, their formulations, and their synergistic combination with immune checkpoint inhibitors in cancer immunotherapy.