Combination strategies with PD-1/PD-L1 blockade: current advances and future directions

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Jan. 21, 2022

Antibodies targeting programmed cell death protein-1 (PD-1) or its ligand PD-L1 rescue T cells from exhausted status and revive immune response against cancer cells. Based on the immense success in clinical trials, ten α-PD-1 (nivolumab, pembrolizumab, cemiplimab, sintilimab, camrelizumab, toripalimab, tislelizumab, zimberelimab, prolgolimab, dostarlimab) three α-PD-L1 antibodies (atezolizumab, durvalumab, avelumab) have been approved for various types of cancers. Nevertheless, low rate α-PD-1/PD-L1 therapy remains to be resolved. For most patients, PD-1/PD-L1 pathway is not sole speed-limiting factor antitumor immunity, it insufficient motivate effective by blocking axis. It has validated that some combination therapies, including plus chemotherapy, radiotherapy, angiogenesis inhibitors, targeted therapy, other checkpoint agonists co-stimulatory molecule, stimulator interferon genes agonists, fecal microbiota transplantation, epigenetic modulators, metabolic superior efficacies higher rates. Moreover, bifunctional bispecific containing moiety also elicited more potent activity. These strategies simultaneously boost multiple processes cancer-immunity cycle, remove immunosuppressive brakes, orchestrate an immunosupportive tumor microenvironment. In this review, we summarized synergistic mechanisms with therapies. focused advances α-PD-1/PD-L1-based immunomodulatory studies. Given heterogeneity across patients types, individualized selection could improve effects relieve treatment resistance.

Language: Английский

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Neoantigens: promising targets for cancer therapy

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Jan. 6, 2023

Abstract Recent advances in neoantigen research have accelerated the development and regulatory approval of tumor immunotherapies, including cancer vaccines, adoptive cell therapy antibody-based therapies, especially for solid tumors. Neoantigens are newly formed antigens generated by cells as a result various tumor-specific alterations, such genomic mutation, dysregulated RNA splicing, disordered post-translational modification, integrated viral open reading frames. recognized non-self trigger an immune response that is not subject to central peripheral tolerance. The quick identification prediction neoantigens been made possible advanced next-generation sequencing bioinformatic technologies. Compared tumor-associated antigens, highly immunogenic provide emerging targets personalized serve prospective predictors survival prognosis checkpoint blockade responses. therapies will be aided understanding mechanism underlying neoantigen-induced anti-tumor streamlining process neoantigen-based immunotherapies. This review provides overview on characterization outlines clinical applications immunotherapeutic strategies based neoantigens. We also explore their current status, inherent challenges, translation potential.

Language: Английский

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Evolving therapeutic landscape of advanced hepatocellular carcinoma

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2022, Volume and Issue: 20(4), P. 203 - 222

Published: Nov. 11, 2022

Language: Английский

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CAR race to cancer immunotherapy: from CAR T, CAR NK to CAR macrophage therapy

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

Published: March 31, 2022

Abstract Adoptive cell therapy with chimeric antigen receptor (CAR) immunotherapy has made tremendous progress five CAR T therapies approved by the US Food and Drug Administration for hematological malignancies. However, in solid tumors lags significantly behind. Some of major hurdles include manufacturing, lack tumor-specific antigens, inefficient trafficking infiltration into tumor sites, immunosuppressive microenvironment (TME), therapy-associated toxicity, escape. Natural Killer (NK) cells have several advantages over as NK can be manufactured from pre-existing lines or allogeneic unmatched histocompatibility complex (MHC); kill cancer through both CAR-dependent CAR-independent pathways; less especially cytokine-release syndrome neurotoxicity. At least one clinical trial showed efficacy tolerability therapy. Macrophages efficiently infiltrate tumors, are immune regulators abundantly present TME. The M2 macrophages at efficient proinflammatory M1 phagocytosis target cells; induced to differentiate phenotype. Consequently, there is significant interest developing overcome some associated T/NK therapy, tumors. Nevertheless, their own limitations. This comprehensive review article will discuss current status followed structure cutting-edge research cancer-specific phagocytes, presenters, immunostimulators, TME modifiers.

Language: Английский

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Immunotherapy: Reshape the Tumor Immune Microenvironment

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

Published: July 6, 2022

Tumor immune microenvironment (TIME) include tumor cells, cytokines, etc. The interactions between these components, which are divided into anti-tumor and pro-tumor, determine the trend of immunity. Although system can eliminate through cancer-immune cycle, tumors appear to eventually evade from surveillance by shaping an immunosuppressive microenvironment. Immunotherapy reshapes TIME restores killing ability cells. Herein, we review function cells within discuss contribution current mainstream immunotherapeutic approaches remolding TIME. Changes in different forms under intervention immunotherapy shed light on better combination treatment strategies.

Language: Английский

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Myeloid-derived suppressor cells: an emerging target for anticancer immunotherapy

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Sept. 26, 2022

Abstract The clinical responses observed following treatment with immune checkpoint inhibitors (ICIs) support immunotherapy as a potential anticancer treatment. However, large proportion of patients cannot benefit from it due to resistance or relapse, which is most likely attributable the multiple immunosuppressive cells in tumor microenvironment (TME). Myeloid-derived suppressor (MDSCs), heterogeneous array pathologically activated immature cells, are chief component networks. These potently suppress T-cell activity and thus contribute escape malignant tumors. New findings indicate that targeting MDSCs might be an alternative promising target for immunotherapy, reshaping enhancing efficacy cancer immunotherapy. In this review, we focus primarily on classification inhibitory function crosstalk between other myeloid cells. We also briefly summarize latest approaches therapies MDSCs.

Language: Английский

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Tumor organoids: applications in cancer modeling and potentials in precision medicine

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: May 12, 2022

Abstract Cancer is a top-ranked life-threatening disease with intratumor heterogeneity. Tumor heterogeneity associated metastasis, relapse, and therapy resistance. These factors contribute to treatment failure an unfavorable prognosis. Personalized tumor models faithfully capturing the of individual patients are urgently needed for precision medicine. Advances in stem cell culture have given rise powerful organoid technology generation vitro three-dimensional tissues that been shown more accurately recapitulate structures, specific functions, molecular characteristics, genomic alterations, expression profiles, microenvironment primary tumors. Tumoroids serve as important component pipeline discovery potential therapeutic targets identification novel compounds. In this review, we will summarize recent advances tumoroid cultures excellent tool accurate cancer modeling. Additionally, vascularization immune modeling based on also be described. Furthermore, great organoids predicting response, investigating resistance-related mechanisms, optimizing strategies, exploring therapies. addition, bottlenecks challenges current tumoroids discussed review.

Language: Английский

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Research progress on dendritic cell vaccines in cancer immunotherapy

Experimental Hematology and Oncology, Journal Year: 2022, Volume and Issue: 11(1)

Published: Jan. 24, 2022

Dendritic cell (DC) vaccines induce specific immune responses that can selectively eliminate target cells. In recent years, many studies have been conducted to explore DC vaccination in the treatment of hematological malignancies, including acute myeloid leukemia and myelodysplastic syndromes, as well other nonleukemia malignancies. There are at least two different strategies use DCs promote antitumor immunity: situ canonical vaccination. Monocyte-derived (mo-DCs) leukemia-derived (DCleu) main types used for AML MDS thus far. Different cancer-related molecules such peptides, recombinant proteins, apoptotic leukemic cells, whole tumor cells or lysates DCs/DCleu containing a vaster antigenic repertoire with RNA electroporation, antigen sources load DCs. To enhance vaccine efficacy, new strategies, combination conventional chemotherapy, monospecific/bispecific antibodies checkpoint-targeting therapies, explored. After decade trials tribulations, much progress has made promise emerged field. this review we summarize advances immunotherapy AML/MDS

Language: Английский

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Recent advances in targeted strategies for triple-negative breast cancer

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: Aug. 28, 2023

Triple-negative breast cancer (TNBC), a highly aggressive subtype of cancer, negatively expresses estrogen receptor, progesterone and the human epidermal growth factor receptor 2 (HER2). Although chemotherapy is main form treatment for patients with TNBC, effectiveness TNBC still limited. The search more effective therapies urgent. Multiple targeted therapeutic strategies have emerged according to specific molecules signaling pathways expressed in TNBC. These include PI3K/AKT/mTOR inhibitors, Notch poly ADP-ribose polymerase antibody-drug conjugates. Moreover, immune checkpoint example, pembrolizumab, atezolizumab, durvalumab, are widely explored clinic. We summarize recent advances therapy immunotherapy aim serving as reference development individualized future.

Language: Английский

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Metabolic profiles of regulatory T cells and their adaptations to the tumor microenvironment: implications for antitumor immunity

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: Aug. 10, 2022

Abstract Characterized by the expression of critical transcription factor forkhead box protein P3, regulatory T (Treg) cells are an essential part immune system, with a dual effect on pathogenesis autoimmune diseases and cancer. Targeting Tregs to reestablish proinflammatory immunogenic tumor microenvironment (TME) is increasingly attractive strategy for cancer treatment has been emphasized in recent years. However, attempts have significantly hindered subsequent autoimmunity after Treg ablation owing systemic loss their suppressive capacity. Cellular metabolic reprogramming acknowledged as hallmark cancer, emerging evidence suggests that elucidating underlying mechanisms how intratumoral acquire fitness superior immunosuppression TME may contribute clinical benefits. In this review, we discuss common distinct profiles peripheral tissues TME, well differences between other conventional preferences. By focusing roles different programs, such glycolysis, oxidative phosphorylation, fatty acid oxidation, synthesis, amino metabolism, regulators modulating proliferation, migration, function, hope provide new insights into cell-targeted antitumor immunotherapies.

Language: Английский

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