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immune checkpoint inhibitors

Immune checkpoint inhibitors are a category of immunotherapy medications used in cancer treatment. Their primary function is to mobilize the body's immune system to identify and attack cancer cells effectively. This is achieved by blocking specific proteins called immune checkpoint proteins that can otherwise suppress the body's immune response.

Within the immune system, there are natural regulatory mechanisms, often referred to as immune checkpoints, designed to maintain balance and prevent excessive immune reactions. These mechanisms include proteins like CTLA-4 (Cytotoxic T-Lymphocyte Antigen 4) and PD-1 (Programmed Cell Death Protein 1) on immune cells, as well as their corresponding ligands PD-L1 and PD-L2 on tumor cells.

Cancer cells can take advantage of these checkpoint proteins to avoid detection by the immune system. They may increase the expression of checkpoint ligands like PD-L1, which bind to immune checkpoint receptors on T cells. This interaction essentially "shuts off" the immune response against the cancer.

Immune checkpoint inhibitors are specialized monoclonal antibodies designed to disrupt these interactions. For instance, drugs such as ipilimumab target CTLA-4, while others like pembrolizumab and nivolumab block PD-1. By blocking these interactions, these inhibitors "release the brakes" on the immune system, allowing T cells to recognize and attack cancer cells.

These drugs have gained approval for treating various cancers, including melanoma, lung cancer, bladder cancer, kidney cancer, and specific lymphomas, among others. They have demonstrated remarkable success in some cases, leading to long-lasting responses and extended periods of remission.

However, the effectiveness of immune checkpoint inhibitors varies among patients, depending on factors such as the type of cancer, the level of checkpoint protein expression, and the patient's overall immune health.

Despite their potential benefits, immune checkpoint inhibitors can lead to immune-related side effects, often termed immune-related adverse events (irAEs). These side effects can affect various organs and systems and necessitate careful monitoring and management.

Researchers are actively exploring combination therapies involving multiple immune checkpoint inhibitors or combining them with other treatments like chemotherapy, radiation therapy, or targeted therapy to improve response rates and minimize side effects.

The development and application of immune checkpoint inhibitors represent a significant advancement in cancer treatment, and ongoing research aims to expand their use to more cancer types while refining their application. Additionally, scientists are investigating novel checkpoint proteins and pathways as potential targets for future therapies.

Citation:

Magnetic Resonance Colonography Enables the Efficacy Assessment of Immune Checkpoint Inhibitors in an Orthotopic Colorectal Cancer Mouse Model Keratinocyte differentiation antigen-specific T cells in immune checkpoint inhibitor-treated NSCLC patients are associated with improved survival


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