PD-1 and PD-L1: architects of immune symphony and immunotherapy breakthroughs in cancer treatment

Abstract

PD-1 (Programmed Cell Death Protein-1) and PD-L1 (Programmed Cell Death Ligand-1) play a crucial role in regulating the immune system and preventing autoimmunity. Cancer cells can manipulate this system, allowing them to escape immune detection and promote tumor growth. Therapies targeting the PD-1/PD-L1 pathway have transformed cancer treatment and have demonstrated significant effectiveness against various cancer types. This study delves into the structure and signaling dynamics of PD-1 and its ligands PD-L1/PD-L2, the diverse PD-1/PD-L1 inhibitors and their efficacy, and the resistance observed in some patients. Furthermore, this study explored the challenges associated with the PD-1/PD-L1 inhibitor treatment approach. Recent advancements in the combination of immunotherapy with chemotherapy, radiation, and surgical procedures to enhance patient outcomes have also been highlighted. Overall, this study offers an in-depth overview of the significance of PD-1/PD-L1 in cancer immunotherapy and its future implications in oncology.

Immune-Related Peripheral Neuropathy Associated with Immune Checkpoint Inhibitors: Case Report and Review of Literature

“…However, due to their mechanism of action, they are frequently associated with the occurrence of immune-related adverse events (irAEs), which can vary in onset and severity. These events have been described in up to 90% of those receiving anti-CTLA-4 antibodies and 70% of those receiving anti-PD-1/PD-L1, and they are severe ( grade ≥ 3) in approximately 20% of patients [ 2 ].…”

“…Antitumor immunotherapy with immune checkpoint inhibitors (ICIs) represents a new cornerstone in oncology treatment, as it has demonstrated improvement in the outcomes in multiple cancers, including cholangiocarcinoma [ 1 ]. The mechanism of action of these drugs involves immune checkpoint blockade, enhancing antitumor immunity by inhibiting intrinsic suppressors of the immune system, such as cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD-1), or its ligand PD-L1 [ 2 ].…”

PTMs of PD-1/PD-L1 and PROTACs application for improving cancer immunotherapy

“…Many types of cancer cells exploit this pathway by overexpressing PD-L1. When cancer cells present high levels of PD-L1, they can bind to PD-1 receptors on T cells, effectively “turning off” these immune cells and preventing them from attacking the cancer ( 87 ). Given the role of the PD-1/PD-L1 pathway in allowing cancer cells to evade the immune system, blocking this interaction has become a key strategy in cancer immunotherapy ( 88 ).…”

Rationale for immune checkpoint inhibitors plus targeted therapy for advanced renal cell carcinoma

“…In the therapy of ICIs, the downregulation of cellular immune responses in TME is able to be held back by the interaction between PD-1 on T cells and its ligand (PD-L1) on tumor cells [ 98 ]. For instance, there is a humanized monoclonal antibody named atezolizumab, which has capability to enhance anti-cancer immunity by inhibiting the interplay between PD-L1 and its receptors PD-1 and B7-1 as a blocker of programmed cell death-ligand (PD-L1) [ 99 ].…”