The future of cancer immunotherapy: microenvironment-targeting combinations

Cell Research, Год журнала: 2020, Номер 30(6), С. 507 - 519

Опубликована: Май 28, 2020

Abstract Immunotherapy holds the potential to induce durable responses, but only a minority of patients currently respond. The etiologies primary and secondary resistance immunotherapy are multifaceted, deriving not from tumor intrinsic factors, also complex interplay between cancer its microenvironment. In addressing frontiers in clinical immunotherapy, we describe two categories approaches design novel drugs combination therapies: first involves direct modification tumor, while second indirectly enhances immunogenicity through alteration By systematically factors that mediate resistance, able identify mechanistically-driven improve outcomes.

Язык: Английский

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Myeloid-derived suppressor cells as immunosuppressive regulators and therapeutic targets in cancer

Signal Transduction and Targeted Therapy, Год журнала: 2021, Номер 6(1)

Опубликована: Окт. 7, 2021

Abstract Myeloid-derived suppressor cells (MDSCs) are a heterogenic population of immature myeloid with immunosuppressive effects, which undergo massive expansion during tumor progression. These not only support immune escape directly but also promote invasion via various non-immunological activities. Besides, this group proved to impair the efficiency current antitumor strategies such as chemotherapy, radiotherapy, and immunotherapy. Therefore, MDSCs considered potential therapeutic targets for cancer therapy. Treatment targeting have shown promising outcomes in both preclinical studies clinical trials when administrated alone, or combination other anticancer therapies. In review, we shed new light on recent advances biological characteristics functions MDSCs. We hope propose an overview MDSCs-targeting therapies so provide ideas treatment.

Язык: Английский

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PD-1 and PD-L1 in cancer immunotherapy: clinical implications and future considerations

Human Vaccines & Immunotherapeutics, Год журнала: 2019, Номер 15(5), С. 1111 - 1122

Опубликована: Март 19, 2019

Programmed death-1 (PD-1) is a cell surface receptor that functions as T checkpoint and plays central role in regulating exhaustion. Binding of PD-1 to its ligand, programmed death-ligand 1 (PD-L1), activates downstream signaling pathways inhibits activation. Moreover abnormally high PD-L1 expression on tumor cells antigen-presenting the microenvironment mediates immune escape, development anti-PD-1/PD-L1 antibodies has recently become hot topic cancer immunotherapy. Here, we review structure PD-L1, function PD-1/PD-L1 pathway, application or monoclonal future directions for with combination therapies. Cancer immunotherapy using blockade may require more studies, this approach be curative patients many types future.

Язык: Английский

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Human Disease Ontology 2018 update: classification, content and workflow expansion

Nucleic Acids Research, Год журнала: 2018, Номер 47(D1), С. D955 - D962

Опубликована: Окт. 22, 2018

The Human Disease Ontology (DO) (http://www.disease-ontology.org), database has undergone significant expansion in the past three years. DO disease classification includes specific formal semantic rules to express meaningful models and expanded from a single asserted include multiple-inferred mechanistic classifications, thus providing novel perspectives on related diseases. Expansion of terms, alternative anatomy, cell type genetic classifications workflow automation highlight updates for since 2015. enhanced breadth depth DO's knowledgebase utility exploring multi-etiology human disease, improving capture communication health-related data across biomedical databases, bioinformatics tools, genomic cancer resources demonstrated by 6.6× growth user community continual integration knowledge, evidenced more than 200 SVN/GitHub releases/revisions, previously reported our 2015 NAR paper, addition 2650 new 30% increase textual definitions, an expanding suite hierarchies constructed through defined logical axioms.

Язык: Английский

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IL4I1 Is a Metabolic Immune Checkpoint that Activates the AHR and Promotes Tumor Progression

Cell, Год журнала: 2020, Номер 182(5), С. 1252 - 1270.e34

Опубликована: Авг. 19, 2020

Aryl hydrocarbon receptor (AHR) activation by tryptophan (Trp) catabolites enhances tumor malignancy and suppresses anti-tumor immunity. The context specificity of AHR target genes has so far impeded systematic investigation activity its upstream enzymes across human cancers. A pan-tissue signature, derived natural language processing, revealed that 32 entities, interleukin-4-induced-1 (IL4I1) associates more frequently with than IDO1 or TDO2, hitherto recognized as the main Trp-catabolic enzymes. IL4I1 activates through generation indole metabolites kynurenic acid. It reduced survival in glioma patients, promotes cancer cell motility, adaptive immunity, thereby enhancing progression chronic lymphocytic leukemia (CLL) mice. Immune checkpoint blockade (ICB) induces IL4I1. As inhibitors do not block IL4I1, may explain failure clinical studies combining ICB inhibition. Taken together, opens new avenues for therapy.

Язык: Английский

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Signal pathways of melanoma and targeted therapy

Signal Transduction and Targeted Therapy, Год журнала: 2021, Номер 6(1)

Опубликована: Дек. 20, 2021

Abstract Melanoma is the most lethal skin cancer that originates from malignant transformation of melanocytes. Although melanoma has long been regarded as a cancerous malignancy with few therapeutic options, increased biological understanding and unprecedented innovations in therapies targeting mutated driver genes immune checkpoints have substantially improved prognosis patients. However, low response rate inevitable occurrence resistance to currently available targeted posed obstacle path management obtain further amelioration. Therefore, it necessary understand mechanisms underlying pathogenesis more comprehensively, which might lead substantial progress approaches expand clinical options for therapy. In this review, we firstly make brief introduction epidemiology, subtypes, risk factors, current therapies. Then, signal pathways orchestrating pathogenesis, including genetic mutations, key transcriptional regulators, epigenetic dysregulations, metabolic reprogramming, crucial metastasis-related signals, tumor-promoting inflammatory pathways, pro-angiogenic systemically reviewed discussed. Subsequently, outline progresses checkpoints, well treatment resistance. Finally, prospects challenges development therapy, especially immunotherapy related ongoing trials, are summarized

Язык: Английский

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Immune control by amino acid catabolism during tumorigenesis and therapy

Nature reviews. Cancer, Год журнала: 2019, Номер 19(3), С. 162 - 175

Опубликована: Янв. 29, 2019

Язык: Английский

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Next-generation immuno-oncology agents: current momentum shifts in cancer immunotherapy

Journal of Hematology & Oncology, Год журнала: 2020, Номер 13(1)

Опубликована: Апрель 3, 2020

Abstract Cancer immunotherapy has reached a critical point, now that immune checkpoint inhibitors and two CAR-T products have received market approval in treating 16 types of cancers 1 tissue-agnostic cancer indication. Accompanying these advances, the 2018 Nobel Prize was awarded for discovery pathways, which led to revolution anti-cancer treatments. However, expanding indications immuno-oncology agents overcoming treatment resistance face mounting challenges. Although combination is an obvious strategy pursue, fact there been more failures than successes this effort served as wake-up call, placing emphasis on importance building solid scientific foundation development next-generation (IO) agents. The 2019 China Immunotherapy Workshop held discuss current challenges opportunities IO. At conference, emerging concepts strategies IO were proposed, focusing squarely correcting immunological defects tumor microenvironment. New targets such Siglec-15 new directions including neoantigens, vaccines, oncolytic viruses, cytokines reviewed. Emerging immunotherapies discussed areas primary secondary existing inhibitors, activating effector cells, targeting immunosuppressive mechanisms In article, we highlight old waves therapy development, provide perspectives latest momentum shifts immunotherapy.

Язык: Английский

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Amino Acids and Their Transporters in T Cell Immunity and Cancer Therapy

Molecular Cell, Год журнала: 2020, Номер 80(3), С. 384 - 395

Опубликована: Сен. 29, 2020

Язык: Английский

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Overcoming immunotherapy resistance in non-small cell lung cancer (NSCLC) - novel approaches and future outlook

Molecular Cancer, Год журнала: 2020, Номер 19(1)

Опубликована: Сен. 11, 2020

Abstract Immunotherapy (IO) has revolutionized the therapy landscape of non-small cell lung cancer (NSCLC), significantly prolonging overall survival (OS) advanced stage patients. Over recent years IO been broadly integrated into first-line setting non-oncogene driven NSCLC, either in combination with chemotherapy, or selected patients PD-L1 high expression as monotherapy. Still, a significant proportion suffer from disease progression. A better understanding resistance mechanisms depicts central goal to avoid overcome and improve patient outcome. We here review major cellular molecular pathways within tumor microenvironment (TME) that may impact evolution resistance. summarize upcoming treatment options after including novel targets (e.g. RIG-I, STING) well interesting combinational approaches such combined anti-angiogenic agents metabolic IDO-1, adenosine signaling, arginase). By discussing fundamental mode action TME, we aim understand manage seed new ideas for effective therapeutic concepts.

Язык: Английский

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