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In the cancer disease state, the interaction of PD-L1 on the tumor cells with PD-1 on a T-cell reduces T-cell function signals to prevent the immune system from attacking the tumor cells. [9] Use of an inhibitor that blocks the interaction of PD-L1 with the PD-1 receptor can prevent the cancer from evading the immune system in this way. [ 9 ]
PD-L1 binds to its receptor, PD-1, found on activated T cells, B cells, and myeloid cells, to modulate activation or inhibition. The affinity between PD-L1 and PD-1, as defined by the dissociation constant K d, is 770 nM. PD-L1 also has an appreciable affinity for the costimulatory molecule CD80 (B7-1), but not CD86 (B7-2). [11]
PD-L1 expression on the surface on cancer cells plays a significant role. PD-L1 positive tumors were twice as likely to respond to combination treatment. [38] [37] However patients with PD-L1 negative tumors also have limited response to anti-PD1, demonstrating that PD-L1 expression is not an absolute determinant of the effectiveness of therapy ...
Micrograph showing a PD-L1 positive non-small cell lung carcinoma. PD-L1 immunostain. As of 2019, pembrolizumab is used via intravenous infusion to treat inoperable or metastatic melanoma, metastatic non-small cell lung cancer (NSCLC) in certain situations, as a first-line treatment for metastatic bladder cancer in patients who cannot receive cisplatin-based chemotherapy and have high levels ...
Among PD-L1 functions is a key regulatory role on T cell activities. It appears that (cancer-mediated) upregulation of PD-L1 on the cell surface may inhibit T cells that might otherwise attack. PD-L1 on cancer cells also inhibits FAS- and interferon-dependent apoptosis, protecting cells from cytotoxic molecules produced by T cells.
Summit Therapeutics (NASDAQ: SMMT) has risen in prominence in the past two years thanks to a promising pipeline candidate, ivonescimab, a potential cancer treatment. It doesn't have a single drug ...
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