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Role of Nanoparticles in Cancer Immunotherapy
Published in D. Sakthi Kumar, Aswathy Ravindran Girija, Bionanotechnology in Cancer, 2023
Immunotherapy mediated by blockade of immunoinhibitory receptors programmed cell death 1 (PD-1) and CTLA-4 that reactivates T cells and clears the antigen/tumor load. Cancer immunotherapy surpassed the contemporary treatment methods in improved survival, efficacy, and applicability to a wide range of tumors irrespective of their origin and type. The beauty of cancer immunotherapy lies in the fact that it not only treats the primary cancer, but can also prevent metastasis and recurrence of the tumor post-treatment. Because of several advantages over other treatment methods, PD-1 blockade-based cancer immunotherapy has led to a paradigm shift in cancer treatment. In 2018, the most prestigious award ‘Nobel Prize’ in ‘Medicine’ for the discovery of PD-1 and CTLA-4 was awarded jointly to Prof. Tasuku Honjo and Prof. J.P. Allison [23]. Summary of the difference between immune checkpoint blockade-based cancer immunotherapy and other standard therapies is given in Table 12.1.
Lung Matters
Published in Namrita Lall, Medicinal Plants for Cosmetics, Health and Diseases, 2022
PDL-1 is found on normal cells and attaches to PD-1 found on T cells, thus turning off the immune response which occurs naturally when a response is no longer needed. However, cancer cells can also express PDL-1, thereby turning off the immune response and preventing the immune system from attacking the tumor. PDL-1 inhibitors attach to PD-1 on T cells, and PD-1 inhibitors attach to PD-1 on cancer cells. Both these inhibitors stop cancer cells with PDL-1 from attaching to T cells, thus enabling T cells to attack the cancer cells. Examples of PDL-1 inhibitors that are approved for use in NSCLC include Atezolizumab, Durvalumab, Nivolumab and Pembrolizumab (Alder, 2017). Studies have indicated that SCLC has a lower rate of PDL-1 expression than NSCLC (Sloan et al., 2016).
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.
Combination of two novel blocking antibodies, anti-PD-1 antibody ezabenlimab (BI 754091) and anti-LAG-3 antibody BI 754111, leads to increased immune cell responses
Published in OncoImmunology, 2022
Markus Zettl, Melanie Wurm, Otmar Schaaf, Sven Mostböck, Iñigo Tirapu, Ilse Apfler, Ivo C. Lorenz, Lee Frego, Cynthia Kenny, Michael Thibodeau, Elisa Oquendo Cifuentes, Markus Reschke, Jürgen Moll, Norbert Kraut, Anne Vogt, Jonathon D. Sedgwick, Irene C. Waizenegger
Programmed cell death protein-1 (PD-1) and its ligands, PD-L1 and PD-L2, are key factors in controlling immune responses.1,2 Engagement of PD-1 by its ligands negatively regulates the T-cell immune response, preventing damage to healthy tissue. However, tumors can leverage the PD-1 signaling pathway to evade immune-mediated destruction.3 Tumor-infiltrating lymphocytes from patients with cancer often express high levels of PD-1, while tumor cells and other cells in the tumor tissue can upregulate PD-L1 expression.4 Blocking the interaction between PD-1 and its ligands activates T-cell function and promotes tumor cell death.3,5–8 Antibodies targeting PD-1 or PD-L1 have revolutionized the treatment of a variety of cancer types; however, not all patients respond to these therapies.9 Therefore, current research is focused on identifying patient selection biomarkers and understanding resistance mechanisms. Alterations within the interferon-γ (IFN-γ) signaling pathway and the antigen presentation machinery of tumor cells, as well as upregulation of other inhibitory co-receptors, such as lymphocyte activation gene-3 (LAG-3), have been identified as potential escape mechanisms.10–13
Pembrolizumab as a single agent for patients with MSI-H advanced endometrial carcinoma
Published in Expert Review of Anticancer Therapy, 2022
Margherita Turinetto, Valentina Lombardo, Carmela Pisano, Lucia Musacchio, Sandro Pignata
T-cells play a pivotal role in immune responses against neoplasms. Antigen-specific T-cells are generated and clonally expanded on antigenic stimulation, consequently acquiring effector functions. However, if antigenic stimulation is prolonged, T-cells might lose their effector functions even in the presence of the targeted antigens. Such inhibition is supported by immune checkpoints, which provide regulatory feedback mechanisms to limit the effector phase of T-cell functions and expansion [15]. Immune checkpoints include various molecules, of which PD-L1 and PD-L2 are two of the most important. PD-L1/2 are transmembrane proteins that can inhibit immune cells by binding to their receptor, the PD-1 [29]. PD-1 is expressed on activated CD4+ and CD8 + T-cells, B-cells, natural killer cells, macrophages, and dendritic cells [30]. PD-L1/2 is expressed on the neoplastic cells of many different cancers. The binding to PD-1 on T-cells leads to immune suppression. Indeed, PD-L1/2 expression is a major mechanism by which tumor cells can evade immune attacks [14,29].
Efficacy of nivolumab as second line treatment for recurrent or metastatic head and neck squamous cell carcinoma: a national DAHANCA cohort study
Published in Acta Oncologica, 2022
Sebastian Søby, Anita Gothelf, Niels Gyldenkerne, Jens Bentzen, Kinga Nowicka-Matus, Trine Tramm, Jesper Grau Eriksen
Treatment with PD-1 inhibitors is a new and promising palliative treatment for rmHNSCC often with lower morbidity than classical chemotherapy [4,5]. Common side effects related to PD-1 inhibition include fatigue, nausea, rash, decreased appetite, and pruritus [4]. However, the available studies investigating the efficacy of PD-1 inhibitors have only included a highly selected group of relatively young patients in good general condition, and these do not necessarily reflect the typical real-life patient. Such patients are often older, present with substantial comorbidity, as well as impaired WHO performance status [6]. Furthermore, the difference in treatment response appears to differ greatly between patients [4]. For this reason, identification of clinical, as well as biological, factors affecting the individual response to the treatment would be valuable for patient selection.