Diversity of immune checkpoints in cancer immunotherapy

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: March 7, 2023

Finding effective treatments for cancer remains a challenge. Recent studies have found that the mechanisms of tumor evasion are becoming increasingly diverse, including abnormal expression immune checkpoint molecules on different cells, in particular T natural killer macrophages and others. In this review, we discuss with enhanced these lymphocytes their consequences effector functions. Dissecting diverse roles checkpoints cells is crucial full understanding immunotherapy using inhibitors.

Language: Английский

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Novel gene manipulation approaches to unlock the existing bottlenecks of CAR-NK cell therapy

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 12

Published: Feb. 11, 2025

Currently, CAR-T cell therapy is known as an efficacious treatment for patients with relapsed/refractory hematologic malignancies. Nonetheless, this method faces several bottlenecks, including low efficacy solid tumors, lethal adverse effects, high cost of autologous products, and the risk GvHD in allogeneic settings. As a potential alternative, CAR-NK can overcome most limitations provide off-the-shelf, safer, more affordable product. Although published results from preclinical clinical studies cells are promising, bottlenecks must be unlocked to maximize effectiveness therapy. These include vivo persistence, trafficking into tumor sites, modest sensitivity immunosuppressive microenvironment. In recent years, advances gene manipulation tools strategies have laid groundwork current This review will introduce existing discuss their advantages disadvantages. We also explore how these enhance therapy’s safety efficacy.

Language: Английский

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NK Cell Dysfunction and Checkpoint Immunotherapy

Frontiers in Immunology, Journal Year: 2019, Volume and Issue: 10

Published: Aug. 21, 2019

NK cells play important roles in the innate immune responses against tumors. The effector function of relies on integration activating and inhibitory signals. Emerging checkpoint receptors molecules are being revealed to mediate cell dysfunction tumor microenvironment. Inhibition some surface has displayed potential reverse tumors, boost anti-tumor immunity, both clinical trials (anti-KIR anti-NKG2A), preclinical studies (e.g. anti-TIGIT, anti-CD96). To fully exploit NK–based immunotherapy, more understanding regional features microenvironment is required. This will provide valuable information regarding dynamic nature response as well novel checkpoints or pathways be targeted. In this Review, we discuss recent advances emerging strategies –based immunotherapy for

Language: Английский

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Immune checkpoint molecules in natural killer cells as potential targets for cancer immunotherapy

Signal Transduction and Targeted Therapy, Journal Year: 2020, Volume and Issue: 5(1)

Published: Oct. 29, 2020

Abstract Recent studies have demonstrated the potential of natural killer (NK) cells in immunotherapy to treat multiple types cancer. NK are innate lymphoid that play essential roles tumor surveillance and control efficiently kill do not require major histocompatibility complex. The discovery NK’s as a promising therapeutic target for cancer is relief oncologists they face challenge increased chemo-resistant cancers. show great against solid hematologic tumors progressively shown promise immunotherapy. effector role these reliant on balance inhibitory activating signals. Understanding various immune checkpoint molecules exhaustion impairment when their receptors excessively expressed particularly important clinical implementation. Emerging been found mediate cell dysfunction microenvironment; this has brought up need explore further additional cell-related checkpoints may be exploited enhance response refractory Accordingly, review will focus recent findings concerning regulation function, well application

Language: Английский

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Targeting immune checkpoints in hematological malignancies

Journal of Hematology & Oncology, Journal Year: 2020, Volume and Issue: 13(1)

Published: Aug. 12, 2020

Immune checkpoint blockade (ICB) therapies such as anti-programmed death 1 (PD-1) and anti-CTLA-4 (cytotoxic T lymphocyte-associated protein 4) have dramatically transformed treatment in solid tumor oncology. While immunotherapeutic approaches stem cell transplantation anti-cancer monoclonal antibodies made critical contributions to improve outcomes hematological malignancies, clinical benefits of ICB are observed only limited types that particularly characterized by a high infiltration immune cells. Importantly, even patients initially respond unable achieve long-term disease control using these therapies. Indeed, primary acquired resistance mechanisms differentially orchestrated malignancies depending on and/or genotypes, thus, an in-depth understanding the disease-specific microenvironments will be essential improving efficacy. In addition PD-1 CTLA-4, various molecules been regulate responses non-redundant manner. Several lines evidence suggest might play unique roles highlighting their potential therapeutic targets. Targeting innate natural killer cells macrophages has also emerged rational approach against tumors resistant cell-mediated immunity. Given surface proteins clinically approved key role augment antibody-mediated cellular cytotoxicity phagocytosis. this review, we discuss recent advances emerging malignancies.

Language: Английский

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