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Oncogenesis and Metastasis
Published in Karl H. Pang, Nadir I. Osman, James W.F. Catto, Christopher R. Chapple, Basic Urological Sciences, 2021
Immune checkpoint blockade forms the basis of immunotherapy.PD-L1 (programmed cell death protein ligand 1) on tumour cells.PD-1 (programmed cell death protein 1) on T-cells.PD-L1 and PD-1 binding results in T-cell deactivation.PD-L1 and/or PD-1 inhibitor are used in metastatic bladder/renal cancers.CTLA-4 (cytotoxic T-lymphocyte associated protein 4).Expressed by regulatory T-cells.CTLA-4 inhibitors are used in metastatic renal cancer.Inhibitors restore tumour-specific T-cell immunity.
Biomarkers for the Immune Checkpoint Inhibitors
Published in Sherry X. Yang, Janet E. Dancey, Handbook of Therapeutic Biomarkers in Cancer, 2021
Weijie Ma, Sixi Wei, Eddie C. Tian, Tianhong Li
The utility of PD-L1 expression as a predictive biomarker varies significantly for various PD-L1 antibodies, scoring systems, positivity cutoffs, and the status for companion versus complementary diagnostics. Table 14.1 summarizes the currently available PD-L1 IHC assays for different ICIs. Several studies have compared and cross-validatedthe available PD-L1 antibodies. Of note, the VENTANA PD-L1 (SP263) assay has been validated to identify NSCLC patients for pembrolizumab [Conformité Européene (CE) mark only, not FDA approved], non-squamous NSCLC patients for nivolumab [CE mark only, not FDA approved], and urothelial carcinoma (UC) patients for durvalumab [FDA approved in the US and CE mark]. Except for SP142, which appears to stain fewer tumor cells and has low sensitivity, the other three assays (SP263, 22C3, and 28–8) have shown comparable analytical performance for detecting PD-L1 expression on tumors cells [23, 24, 104, 105]. Moreover, the new 73–10 assay for PD-L1 expression shows greater sensitivity than all four previous assays (SP263, 22C3, 28–8, and SP142) for predicting clinical response to avelumab in NSCLC [24, 106].
Dopamine and Tumorigenesis in Reproductive Tissues
Published in Nira Ben-Jonathan, Dopamine, 2020
Immunotherapy. Evading antitumor immunity is a hallmark of the emergence and progression of cancer. Tumors employ multiple mechanisms to avoid recognition by the host immune system, including expression of the negative T cell regulatory molecule programmed death ligand-1 (PD-L1). The PD-1 receptor and ligands PD-L1 and PD-L2, which are members of the CD28 and B7 families, play critical roles in T cell co-inhibition and exhaustion [31]. Overexpression of PD-L1 and PD-1 on tumor cells and tumor-infiltrating lymphocytes, respectively, correlates with poor disease outcome in several human cancers. Monoclonal antibodies (mAbs) that block the PD-1/PD-L1 pathway have been developed for cancer immunotherapy via an enhancement of T cell functions. Clinical trials with mAbs to PD-1 and PD-L1 have shown impressive response rates, particularly for melanoma, non-small-cell lung cancer, renal cell carcinoma, and bladder cancer.
Molecular docking study of britannin binding to PD-L1 and related anticancer pseudoguaianolide sesquiterpene lactones
Published in Journal of Receptors and Signal Transduction, 2022
Gérard Vergoten, Christian Bailly
The Programmed Cell Death Protein 1 (PD-1) and its co-inhibitory ligand PD-L1 play a vital role in inhibiting immune responses through modulation of the activity of T-cells and inhibition of apoptosis of regulatory T cells. PD-L1, frequently over-expressed on tumor cells, plays an important role in cancer progression by attenuating the host immune response to tumor cells. Monoclonal antibodies (mAb) targeting PD-L1 or PD-1 are efficient drugs to combat cancer. They can induce durable tumor remissions in patients with diverse advanced cancers, such as non-small cell lung cancers and melanoma for examples [1]. A variety of PD-1/PD-L1 inhibitors have been registered in recent years and other bioproducts are in clinical trials worldwide [2]. These anti-PD-1/PD-L1 mAbs are frequently combined with chemotherapy to reinforce the antitumoral response [3].
Biomarkers for breast cancer immunotherapy: PD-L1, TILs, and beyond
Published in Expert Opinion on Investigational Drugs, 2022
Alessandro Rizzo, Angela Dalia Ricci
In the near future, the BC medical community is called to more efforts aimed at evaluating novel biomarkers of response to ICIs, considering tumor-intrinsic (e.g. TMB, PD-L1 expression, MSI status, etc.), immune-specific, and combinatorial biomarkers – such as PD-L1 plus TMB, TMB, and IFNγ signature, ARID1A plus CXCL13, etc., [81,82]. In fact, although PD-L1 status by immunohistochemistry is considered as the most promising biomarker of response to immunotherapy to date, the predictive ability of PD-L1 expression is far from ideal, and the development of novel, more reliable biomarkers is a crucial need. Based on these premises, a combination of PD-L1 with other predictors would probably be more impactful compared to a single biomarker of response for a better selection of patients. In addition, several novel focuses of research are under active development, including gut microbiome; however, these results appear still far from everyday clinical practice and are still preliminary.
A Nomogram Model to Predict Recurrence of Non-Muscle Invasive Bladder Urothelial Carcinoma After Resection Based on Clinical Parameters and Immunohistochemical Markers
Published in Journal of Investigative Surgery, 2022
Jiangchuan Pi, Yongjiang Xiong, Chuan Liu, Juan Liao, Jiaji Liu, Chuan Li, Wenyu Fu, Tao Zhao
In recent years, cellular immunology therapy, especially the correlation between pathway of programmed cell death receptor-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) and immune escape mechanism has gradually become a hot topic. It has been reported that the high expression level of PD-L1 in bladder cancer patients may be related to disease progression, predicted survival, and risk of death [5]. However, there are few studies on the definite relationship between PD-1 and PD-L1 expression and prognosis of NMIBUC. In addition, PD-L1 does not become a routine screening indicator in clinical practice. In view of practice value, this established model just included these indicators which are commonly used and easily detected in clinical practice to accurately and effectively predict cancer recurrence. But it is necessary that more studies on PD-1 and PD-L1 should be conducted in the future.