Quantifying PD-L1 Expression to Monitor Immune Checkpoint Therapy: Opportunities and Challenges

Nimmagadda, Sridhar

doi:10.3390/cancers12113173

Cited by 38 publications

(41 citation statements)

References 176 publications

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“…PD-1 activation regulates T cell activation, tolerance, and exhaustion, and effector T cell responses. 241,242 Programed death ligand 1 expression can predict a favorable response to antibodies designed to unfetter anti-tumor activity. 243 This means that PD-L1 and its receptor PD-1 represent crucial therapeutic targets to treat cancer as immune checkpoints regulating host immunity.…”

Section: Hormone-based Therapiesmentioning

confidence: 99%

“…They reported that PD-L1 was predictive in only 28.9% of cases and was either not predictive (53.3%) or not tested (17.8%) in the remaining cases. 253 A broad review on this topic has been published by Nimmagadda 241 and Cottrell and Taube. 243 Nonetheless, fortunately, numerous IHC assays have been approved [254][255][256] to detect PD-L1 expression levels for specific drugs; each ICI has its own IHC assay specific to a distinct anti-PD-L1 antibody clone and a particular staining platform with specific tumor cell or immune cell thresholds.…”

Section: Hormone-based Therapiesmentioning

confidence: 99%

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Breast Cancer Therapeutics and Biomarkers: Past, Present, and Future Approaches

Schick

Ritchie

Restini

2021

Breast Cancer�(Auckl)

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Breast cancer (BC) is the leading cause of cancer death in women and the second-most common cancer. An estimated 281 550 new cases of invasive BC will be diagnosed in women in the United States, and about 43 600 will die during 2021. Continual research has shed light on all disease areas, including tumor classification and biomarkers for diagnosis/prognosis. As research investigations evolve, new classes of drugs are emerging with potential benefits in BC treatment that are covered in this manuscript. The initial sections present updated classification and terminology used for diagnosis and prognosis, which leads to the following topics, discussing the past and present treatments available for BC. Our review will generate interest in exploring the complexity of the cell cycle and its association with cancer biology as part of the plethora of target factors toward developing newer drugs and effective therapeutic management of BC.

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Section: Hormone-based Therapiesmentioning

confidence: 99%

Section: Hormone-based Therapiesmentioning

confidence: 99%

Breast Cancer Therapeutics and Biomarkers: Past, Present, and Future Approaches

Schick

Ritchie

Restini

2021

Breast Cancer�(Auckl)

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“…Anti-programmed death 1 activation can stimulate the upregulation of GLUT messenger RNA and GLUT proteins in the tumor microenvironment, leading to glucose consumption and increasing false-positive scanning results (81). The feasibility of using PET to quantify programmed death ligand 1 (PD-L1) levels in patients has been demonstrated with 89 Zr-labeled atezolizumab, but this method still has a high chance of false-positive results, possibly due to inflammation (82). Although there are ongoing clinical trials, there is currently no approved clinical imaging technique for tracking immune cells in humans.…”

Section: Imaging Applications In Monitoring Responses To Immunotherapymentioning

confidence: 99%

Nanotechnology for Cancer Imaging: Advances, Challenges, and Clinical Opportunities

Liu

Grodzinski

2021

Radiology: Imaging Cancer

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Nanoparticle (NP) imaging applications have the potential to improve cancer diagnostics, therapeutics, and treatment management. In biomedical research and clinical practice, NPs can serve as labels or labeled carriers for monitoring drug delivery or serve as imaging agents for enhanced imaging contrast, as well as providing improved signal sensitivity and specificity for in vivo imaging of molecular and cellular processes. These qualities offer exciting opportunities for NP-based imaging agents to address current limitations in oncologic imaging. Despite substantial advancements in NP design and development, very few NP-based imaging agents have translated into clinics within the past 5 years. This review highlights some promising NP-enabled imaging techniques and their potential to address current clinical cancer imaging limitations. Although most examples provided herein are from the preclinical space, discussed imaging solutions could offer unique in vivo tools to solve biologic questions, improve cancer treatment effectiveness, and inspire clinical translation innovation to improve patient care.

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“…Therefore, blocking PD-1 enhances the antitumor activity of the immune system [15]. Studies related to the CTLA-4 protein and the PD-1 receptor are among the most relevant to the treatment of cancer and therefore, many recent reviews in leading biomedical journals have been published [6,14].…”

Section: Introductionmentioning

confidence: 99%

Experimental model and approaches to investigation of the acquired resistance to tumor transplantation in mice

Stoika

2021

Biol. Stud.

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Introduction. An acquired resistance to experimental tumors was detected in animals that recovered from a primary transplanted tumor due to treatment or spontaneously, and demonstrated intolerance to a renewal tumor inoculation. This phenomenon is much less frequently observed, although it is of great scientific interest and medical significance. Here, we have addressed the expression of the resistance phenomenon in a model tumor in mice – Nemeth–Kelner lymphoma (NK/Ly). The aim of our study was to elaborate a reproducible method for induction of resistance to transplantation of lymphoma NK/Ly in mice and to investigate the mechanisms of its development. Methods and Results. Three schemes for induction of resistance were tested. The first one included treatment of tumor-bearing mice with vinblastine and, thereafter, reconvalescent animals were checked for the development of resistance expressed as a complete suppression of tumor growth after re-inoculation of tumor cells. Mice were inoculated intraperitoneally with NK/Ly ascitic cells and then subjected to 2–4 intraperitoneal injections of vinblastine at a dose of 1mg/g of body weight. The recovered mice were re-inoculated with tumor cells and the absence of tumor growth was considered as resistance development. The disadvantage of this approach is that less than 5% of mice achieve a long lasting recovery due to the treatment. The second scheme included the immunization of mice with intraperitoneal injection of the minimal number of viable tumor cells that do not cause tumor growth, but initiate the immune response. However, this approach was not effective, since there was no reliable number of cells corresponding to these demands. The minimal number of 15×103 injected cells per mouse caused a retarded but still progressive tumor growth. In the third scheme, the immunization of mice was conducted by the intraperitoneal injections of NK/Ly cells permeabilized with saponin. It should be noted that treatment with saponin leads to cell death with a minimal damage to cell morphology. The scheme of immunization with permeabilized NK/Ly cells appeared to be simple and effective. It provided a reproducible resistance to transplanted tumor and might be used as a model in studies of the mechanisms of this phenomenon. Cytological investigation of tumor and immunocompetent cells in ascites of control and of tumor-resistant mice was conducted. As revealed, the number of lymphocytes in ascites of tumor-resistant mice was about 4 times higher than such amount in the control (non-resistant) mice. A destruction of tumor cells by the adherent mono-nuclears was observed. Conclusions. The method of induction of resistance to transplantation of experimental tumor NK/Ly by immunization of mice with tumor cells permeabilized with saponin is described. The intraperitoneal inoculation of tumor cells to the tumor-resistant mice caused the marked increase of the mononuclear leukocytes population in the peritoneal fluid, which showed a harmful effect upon tumor cells. Thus, the induction of resistance to transplantation of NK/Ly lymphoma in mice might be provided mainly via the mechanisms of cell immunity, in particular, by the appearance of cytotoxic lymphocytes specific to distinct tumor cells.

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Quantifying PD-L1 Expression to Monitor Immune Checkpoint Therapy: Opportunities and Challenges

Cited by 38 publications

References 176 publications

Breast Cancer Therapeutics and Biomarkers: Past, Present, and Future Approaches

Breast Cancer Therapeutics and Biomarkers: Past, Present, and Future Approaches

Nanotechnology for Cancer Imaging: Advances, Challenges, and Clinical Opportunities

Experimental model and approaches to investigation of the acquired resistance to tumor transplantation in mice

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