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Application of PD-1, PD-L1, and CTLA-4 inhibitors in the treatment of solid tumors: a basic approach in the immunotherapy of oncology diseases

Krum Kafedjiiski, Rostislav Kurdov, Valentina Belcheva


Immune checkpoint proteins like PD-1/PD-L1 and CTLA-4 represent significant scientific discoveries in the immunotherapy of solid tumors. Humanized monoclonal antibodies, known as PD-L1 inhibitors, suppress the binding of PD-L1, a human transmembrane protein referred to as a checkpoint protein. PD-L1 is involved in the signaling of programmed cell death through the receptor PD-1, a cell surface receptor that plays a crucial role in immune system suppression and promotes tolerance to host cells. The two main pathways that are specifically targeted in clinical practice are cytotoxic T-lymphocyte antigen-4 (CTLA-4) and the protein "programmed cell death 1" (PD-1). Humanized monoclonal antibodies targeting these immunological checkpoint proteins have shown success in patients with non-small cell lung cancer (NSCLC), renal cell carcinoma, metastatic melanoma, and head and neck carcinoma. The FDA has approved three categories of immune checkpoint inhibitors: PD-1 inhibitors (Pembrolizumab, Nivolumab, and Cemiplimab), PD-L1 inhibitors (Durvalumab, Atezolizumab, and Avelumab), and CTLA-4 inhibitors (Ipilimumab). Not all patients responded positively, which highlights the role of biomarkers such as PDL-1 expression in predicting the response to immunotherapy with checkpoint inhibitors. This literature review aims to present the latest developments in the field of immunotherapy for the treatment of solid tumors.


PD-1, PD-L1, CTLA-4, immunotherapy

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