Blood-based biomarkers in patients with non-small cell lung cancer treated with immune checkpoint blockade

Journal of Experimental & Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 43(1)

Published: March 16, 2024

Abstract The paradigm of non-small cell lung cancer (NSCLC) treatment has been profoundly influenced by the development immune checkpoint inhibitors (ICI), but range clinical responses observed among patients poses significant challenges. To date, analyses tumor biopsies are only parameter used to guide prognosis ICI therapy. Tumor biopsies, however, often difficult obtain and tissue-based biomarkers limited intratumoral heterogeneity temporal variability. In response, there a growing emphasis on “liquid biopsy”‒ derived biomarkers, which offer minimally invasive means dynamically monitor status NSCLC either before and/or during course treatment. Here we review studies in multiple blood-based encompassing circulating soluble analytes, subsets, DNA, mutational burden, cells have shown promising associations with response These investigations unveiled compelling correlations between peripheral both therapy patient outcomes, include rates, progression-free survival, overall survival. There is need for rigorous validation standardization these assays broader application. Integration into comprehensive panels or algorithms also potential enhance predictive accuracy. Further research aimed at longitudinal monitoring crucial comprehend dynamics resistance mechanisms should be alongside methods that interrogate microenvironment decisions may inform novel therapeutic strategies. data reviewed here reinforce opportunity refine stratification, optimize treatments, improve outcomes not wider spectrum solid tumors undergoing immunotherapy.

Language: Английский

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Soluble Programmed Death Ligand-1 (sPD-L1): A Pool of Circulating Proteins Implicated in Health and Diseases

Cancers, Journal Year: 2021, Volume and Issue: 13(12), P. 3034 - 3034

Published: June 17, 2021

Upon T-cell receptor stimulation, the Programmed cell Death-1 (PD-1) expressed on T-cells can interact with its ligand PD-L1 at surface of cancer cells or antigen-presenting cells. Monoclonal antibodies targeting PD-1 are routinely used for treatment cancers, but their clinical efficacy varies largely across variety tumor types. A part variability is linked to existence several forms PD-L1, either plasma membrane (mPD-L1), secreted cellular exosomes (exoPD-L1), in nuclei (nPD-L1), as a circulating, soluble protein (sPD-L1). Here, we have reviewed different origins and roles sPD-L1 humans highlight biochemical functional heterogeneity protein. isoforms be generated essentially by two non-exclusive processes: (i) proteolysis m/exoPD-L1 metalloproteases, such metalloproteinases (MMP) disintegrin metalloproteases (ADAM), which capable shedding release an active form, (ii) alternative splicing pre-mRNA, leading some cases lacking transmembrane domain. The expression secretion been observed large pathologies, well beyond cancer, notably pulmonary diseases, chronic inflammatory autoimmune disorders, viral diseases. role during pregnancy also evoked. structural proteins, associated functional/cellular plurality, should kept mind when considering biomarker drug target. membrane, exosomal all integral parts highly dynamic PD-1/PD-L1 signaling pathway, essential immune-tolerance immune-escape.

Language: Английский

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A Checkpoint‐Regulatable Immune Niche Created by Injectable Hydrogel for Tumor Therapy

Advanced Functional Materials, Journal Year: 2021, Volume and Issue: 31(37)

Published: June 26, 2021

Abstract Current programmed death‐1 ligand (PD‐L1)‐based therapy focuses on local tumors. However, circulating exosomal PD‐L1 possesses inherent anti‐PD‐L1 blockade resistance and dominates tumor metastasis, playing a critical role in systemic immunosuppression. Therefore, the efficacy of immune checkpoint depends simultaneously decreasing tumoral PD‐L1. such therapeutic platforms have never been reported so far. Herein, checkpoint‐regulatable niche created by an injectable hydrogel is to reprogram both exosomes. Oxidized sodium alginate‐armored membrane vesicle (O‐TMV) as gelator, with Ca 2+ channel inhibitor dimethyl amiloride (DMA) cyclin‐dependent kinase 5 (Cdk5) roscovitine formed (O‐TMV@DR) vivo, work antigen depot create niche. O‐TMV chelates within environment DMA continuously prevents cellular influx, suppressing ‐governed exosome secretion decreased number. Roscovitine not only down‐regulates cell expression along inherited from parental cells via genetic effect, but also blunts cascade connection between up‐regulation interferon‐γ stimulation, achieving down‐regulated full‐scale reprogramming achieved, offering innovative cancer immunotherapy

Language: Английский

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Peripheral Blood-Based Biomarkers for Immune Checkpoint Inhibitors

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(17), P. 9414 - 9414

Published: Aug. 30, 2021

As cancer immunotherapy using immune checkpoint inhibitors (ICIs) is rapidly evolving in clinical practice, it necessary to identify biomarkers that will allow the selection of patients who benefit most or least from ICIs and longitudinally monitor patients’ responses during treatment. Various peripheral blood-based are being identified with recent advances high-throughput multiplexed analytical technologies. The identification these biomarkers, which can be easily detected blood samples non-invasive repeatable methods, contribute overcoming limitations previously used tissue-based biomarkers. Here, we discuss potential circulating cells, soluble inflammatory molecules, tumor cells DNA, exosomes, mutational burden, as for prediction ICI treatment advanced cancer.

Language: Английский

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Macitentan improves antitumor immune responses by inhibiting the secretion of tumor-derived extracellular vesicle PD-L1

Theranostics, Journal Year: 2022, Volume and Issue: 12(5), P. 1971 - 1987

Published: Jan. 1, 2022

Extracellular vesicles (EVs) carrying tumor cell-derived programmed death-ligand 1 (PD-L1) interact with death (PD-1)-producing T cells, thus significantly lowering a patient's response to immune checkpoint blockade drugs.No drug that reinvigorates CD8+ cells by suppressing EV PD-L1 has been approved for clinical usage.Here we have identified macitentan (MAC), an FDA-approved oral drug, as robust booster of antitumor responses in PD-L1.Methods: was analyzed the data from nanoparticle tracking, immunoblotting analyses, and nano-flow cytometry.Antitumor immunity evaluated luciferase assay phenotyping using flow cytometry.Clinical relevance cancer genome atlas database.Results: MAC inhibited secretion tumor-derived targeting endothelin receptor A (ETA) breast xenograft models.MAC enhanced cell-mediated killing decreasing binding PD-1 synergizing effects anti-PD-L1 antibody.MAC also showed anticancer effect triple-negative (TNBC)-bearing immunocompetent mice but not nude mice.The combination therapy antibody improved efficacy increasing cell number activity Treg tumors draining lymph nodes TNBC, colon, lung syngeneic models.The reversed injecting exogenous PD-L1.Notably, ETA level strongly associated innate anti-PD-1 resistance gene signature low PD-1/PD-L1 blockade.Conclusion: These findings demonstrate MAC, already applications, can be used improve and/or overcome inadequate therapy.

Language: Английский

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Extracellular vesicle PD-L1 dynamics predict durable response to immune-checkpoint inhibitors and survival in patients with non-small cell lung cancer

Journal of Experimental & Clinical Cancer Research, Journal Year: 2022, Volume and Issue: 41(1)

Published: June 1, 2022

Abstract Background Immune-checkpoint inhibitors (ICIs) changed the therapeutic landscape of patients with lung cancer. However, only a subset them derived clinical benefit and evidenced need to identify reliable predictive biomarkers. Liquid biopsy is non-invasive repeatable analysis biological material in body fluids promising tool for cancer biomarkers discovery. In particular, there growing evidence that extracellular vesicles (EVs) play an important role tumor progression tumor-immune interactions. Thus, we evaluated whether vesicle PD-L1 expression could be used as biomarker prediction durable treatment response survival non-small cell (NSCLC) undergoing ICIs. Methods Dynamic changes EV were analyzed plasma samples collected before at 9 ± 1 weeks during retrospective prospective independent cohorts 33 39 patients, respectively. Results As result, increase was observed non-responders comparison responders shorter progression-free overall survival. To contrary, tissue expression, commonly biomarker, not neither nor Conclusion These findings indicate dynamics stratify advanced NSCLC who would experience from

Language: Английский

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Interplay between coagulation and inflammation in cancer: Limitations and therapeutic opportunities

Cancer Treatment Reviews, Journal Year: 2021, Volume and Issue: 102, P. 102322 - 102322

Published: Dec. 1, 2021

Advances in understanding the molecular mechanisms of tumor progression have achieved impressive progress treatment cancer and so-called immune checkpoint inhibitors (ICIs) revolutionized therapy. Indeed, antibody-based drugs blocking escape cells by modulation T cell responses are increasingly utilized for a wide range entities. Nonetheless, response rates remain limited, development secondary resistance is common problem. In addition, increasing variety severe side effects provoked. Next to autoimmune responses, activation complement system skin toxicity, an increased incidence thrombotic complications has been observed associated with mortality rate. Based on this, it can be postulated that interplay coagulation inflammation microenvironment relevant each step life cycle. This review focuses as central player fostering progression. Thus, better pathways involved complex interaction circulating cells, plasmatic may help improve therapeutic concepts reducing morbidity cancer.

Language: Английский

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The Key Role of Exosomes on the Pre-metastatic Niche Formation in Tumors

Frontiers in Molecular Biosciences, Journal Year: 2021, Volume and Issue: 8

Published: Sept. 14, 2021

Exosomes or other extracellular vesicles released from cells play an important role in cell-to-cell communication by transferring bio-information (DNA, coding/non-coding RNA, and proteins), which indicates parental cell status to recipient the environment. Increasingly, evidence shows that tumor-derived exosomes mediate tumor pre-metastatic niche (PMN) remodeling establish a supportive receptive promote colonization metastasis. Uptake of genetic information target environment triggers epigenetic changes contribute PMN formation. Here, we provide comprehensive overview current understanding exosomes-mediated reprogramming

Language: Английский

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TGF-β: A novel predictor and target for anti-PD-1/PD-L1 therapy

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Dec. 19, 2022

Transforming growth factor-β (TGF-β) signaling regulates multiple physiological processes, such as cell proliferation, differentiation, immune homeostasis, and wound healing. Besides, TGF-β plays a vital role in diseases, including cancer. Accumulating evidence indicates that controls the composition behavior of components tumor microenvironment (TME). Advanced cancers leverage to reshape TME escape surveillance. TGF-β-mediated evasion is an unfavorable factor for cancer immunotherapy, especially checkpoint inhibitors (ICI). Numerous preclinical clinical studies have demonstrated hyperactive closely associated with ICI resistance. It has been validated blockade synergizes overcomes treatment TGF-β-targeted therapies, trap bispecific antibodies, shown immense potential immunotherapy. In this review, we summarized predictive value prospects therapies

Language: Английский

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Stem cell-derived and circulating exosomal microRNAs as new potential tools for diabetic nephropathy management

Stem Cell Research & Therapy, Journal Year: 2022, Volume and Issue: 13(1)

Published: Jan. 24, 2022

Abstract Background Despite major advances in the treatment of diabetic nephropathy (DN) recent years, it remains most common cause end-stage renal disease. An early diagnosis and therapy may slow down DN progression. Numerous potential biomarkers are currently being researched. Circulating levels kidney-released exosomes biological molecules, which reflect pathology including glomerular tubular dysfunction as well mesangial expansion fibrosis, have shown for predicting occurrence progression DN. Moreover, many experimental therapies investigated, stem cell medications targeting inflammatory, oxidant, or pro-fibrotic pathways activated during The therapeutic cells is partly depending on their secretory capacity, particularly exosomal microRNAs (Exo-miRs). In a growing line research has participation Exo-miRs pathophysiological processes DN, provide effective biomarker tools treatment. Methods A systematic literature search was performed MEDLINE, Scopus, Google Scholar to collect published findings regarding cell-derived circulating DN-associated biomarkers. Findings Glomerular podocytes important culprits pathogenesis and, thus, can be considered valuable targets. Preclinical investigations that exert beneficial effects by transferring renoprotective miRs injured podocytes. Of note, Exo-miR-125a secreted adipose-derived mesenchymal improve cells, while (Exo-miR-486 Exo-miR-215-5p), human urine‐derived (Exo-miR-16-5p), bone marrow-derived (Exo-miR-let-7a) On other hand, clinical indicated isolated from urine serum hold great promising

Language: Английский

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