Targeting immune checkpoints in hematological malignancies DOI Creative Commons
Basit Salik, Mark J. Smyth, Kyohei Nakamura

et al.

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

The history and advances in cancer immunotherapy: understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications DOI Creative Commons
Yuanyuan Zhang, Zemin Zhang

Cellular and Molecular Immunology, Journal Year: 2020, Volume and Issue: 17(8), P. 807 - 821

Published: July 1, 2020

Abstract Immunotherapy has revolutionized cancer treatment and rejuvenated the field of tumor immunology. Several types immunotherapy, including adoptive cell transfer (ACT) immune checkpoint inhibitors (ICIs), have obtained durable clinical responses, but their efficacies vary, only subsets patients can benefit from them. Immune infiltrates in microenvironment (TME) been shown to play a key role development will affect outcomes patients. Comprehensive profiling tumor-infiltrating cells would shed light on mechanisms cancer–immune evasion, thus providing opportunities for novel therapeutic strategies. However, highly heterogeneous dynamic nature TME impedes precise dissection intratumoral cells. With recent advances single-cell technologies such as RNA sequencing (scRNA-seq) mass cytometry, systematic interrogation is feasible provide insights into functional diversities In this review, we outline progress particularly by focusing landmark studies characterization tumor-associated cells, summarize phenotypic connections with immunotherapy. We believe review could strengthen our understanding facilitate elucidation modulation progression, guide immunotherapies treatment.

Language: Английский

Citations

2019
NK cells for cancer immunotherapy DOI
Noriko Shimasaki, Amit Jain, Dario Campana

et al.

Nature Reviews Drug Discovery, Journal Year: 2020, Volume and Issue: 19(3), P. 200 - 218

Published: Jan. 6, 2020

Language: Английский

Citations

965
Natural killer cells in cancer biology and therapy DOI Creative Commons

Song‐Yang Wu,

Tong‐Ming Fu, Yi‐Zhou Jiang

et al.

Molecular Cancer, Journal Year: 2020, Volume and Issue: 19(1)

Published: Aug. 6, 2020

Abstract The tumor microenvironment is highly complex, and immune escape currently considered an important hallmark of cancer, largely contributing to progression metastasis. Named for their capability killing target cells autonomously, natural killer (NK) serve as the main effector toward cancer in innate immunity are heterogeneous microenvironment. Most current treatment options harnessing focus on T cell-immunity, either by promoting activating signals or suppressing inhibitory ones. limited success achieved cell immunotherapy highlights importance developing new-generation immunotherapeutics, example utilizing previously ignored NK cells. Although tumors also evolve resist cell-induced cytotoxicity, cytokine supplement, blockade suppressive molecules genetic engineering may overcome such resistance with great promise both solid hematological malignancies. In this review, we summarized fundamental characteristics recent advances within immunometabolic microenvironment, discussed potential application limitations emerging cell-based therapeutic strategies era presicion medicine.

Language: Английский

Citations

626
Natural killer cells in antitumour adoptive cell immunotherapy DOI Open Access
Tamara Laskowski, Alexander Biederstädt, Katayoun Rezvani

et al.

Nature reviews. Cancer, Journal Year: 2022, Volume and Issue: 22(10), P. 557 - 575

Published: July 25, 2022

Language: Английский

Citations

479
The cancer–natural killer cell immunity cycle DOI
Nicholas D. Huntington, Joseph Cursons, Jai Rautela

et al.

Nature reviews. Cancer, Journal Year: 2020, Volume and Issue: 20(8), P. 437 - 454

Published: June 24, 2020

Language: Английский

Citations

444
The NK cell–cancer cycle: advances and new challenges in NK cell–based immunotherapies DOI
Tobias Bald, Matthew F. Krummel, Mark J. Smyth

et al.

Nature Immunology, Journal Year: 2020, Volume and Issue: 21(8), P. 835 - 847

Published: July 20, 2020

Language: Английский

Citations

371
Roles of natural killer cells in immunity to cancer, and applications to immunotherapy DOI
Natalie K. Wolf, Djem Kissiov, David H. Raulet

et al.

Nature reviews. Immunology, Journal Year: 2022, Volume and Issue: 23(2), P. 90 - 105

Published: May 30, 2022

Language: Английский

Citations

301
Immune checkpoint therapy for solid tumours: clinical dilemmas and future trends DOI Creative Commons
Qian Sun, Zhenya Hong, Cong Zhang

et al.

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

Published: Aug. 28, 2023

Abstract Immune-checkpoint inhibitors (ICBs), in addition to targeting CTLA-4, PD-1, and PD-L1, novel LAG-3 drugs have also been approved clinical application. With the widespread use of drug, we must deeply analyze dilemma agents seek a breakthrough treatment prospect. Over past decades, these demonstrated dramatic efficacy, especially patients with melanoma non-small cell lung cancer (NSCLC). Nonetheless, field broad concept solid tumours, non-specific indications, inseparable immune response side effects, unconfirmed progressive disease, complex regulatory networks resistance are four barriers that limit its Fortunately, successful trials ICB combination therapies, advent era oncolytic virus gene editing, technical mRNA vaccines nano-delivery systems made remarkable breakthroughs currently. In this review, enumerate mechanisms each checkpoint targets, associations between tumour mutation burden, key or signalling pathways, specific evidence efficacy classical targets new among different types put forward dialectical thoughts on drug safety. Finally, discuss importance accurate triage based recent advances predictive biomarkers diagnostic testing techniques.

Language: Английский

Citations

245
Monalizumab: inhibiting the novel immune checkpoint NKG2A DOI Creative Commons
Thorbald van Hall,

Pascale André,

Amir Horowitz

et al.

Journal for ImmunoTherapy of Cancer, Journal Year: 2019, Volume and Issue: 7(1)

Published: Oct. 17, 2019

The implementation of immune checkpoint inhibitors to the oncology clinic signified a new era in cancer treatment. After first indication melanoma, an increasing list additional types are now treated with system targeting antibodies PD-1, PD-L1 and CTLA-4, alleviating inhibition signals on T cells. Recently, we published proof-of-concept results novel inhibitor, NKG2A. This receptor is expressed cytotoxic lymphocytes, including NK cells subsets activated CD8+ Blocking NKG2A unleashed reactivity these effector resulting tumor control multiple mouse models early clinical trial. Monalizumab inhibiting this human beings future trials will have reveal its potency combination other treatment options.

Language: Английский

Citations

236
Risk Factors and Biomarkers for Immune-Related Adverse Events: A Practical Guide to Identifying High-Risk Patients and Rechallenging Immune Checkpoint Inhibitors DOI Creative Commons
Adithya Chennamadhavuni, Laith Abushahin, Ning Jin

et al.

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

Published: April 26, 2022

Immune-related adverse events (irAEs) are a range of complications associated with the use immune-checkpoint inhibitors (ICIs). Two major classes ICIs widely used Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Programmed Cell death-1 (PD-1)/Programmed death-ligand 1 (PD-L1) inhibitors. High-grade irAEs life-threatening often cause severe decline in performance status such that patients do not qualify for any further anticancer treatments. It is difficult to generalize evidence current literature on risk factors or biomarkers entire class as studies so far either disease-specific (e.g., lung cancer melanoma) ICI agent-specific pembrolizumab, ipilimumab) irAE-specific pneumonitis gastritis). In this review, consider before initiating monitoring listed practical purpose day-to-day practice. Risk grouped into demographics social history, medical medication tumor-specific factors. A higher irAE age <60 years, high body mass index, women CTLA4 men PD-1/PD-L1 agents, chronic smokers. Patients significant kidney (Stage IV-V), cardiac (heart failure, coronary artery disease, myocardial infarction, hypertension), (asthma, pulmonary fibrosis, obstructive disease) at respective organ-specific irAEs. Pre-existing autoimmune disease certain drugs (proton pump inhibitors, diuretics, anti-inflammatory drugs) also increase irAE-risk. Biomarkers categorized circulating blood counts, cytokines, autoantibodies, HLA genotypes, microRNA, gene expression profiling, serum proteins. The counts protein markers (albumin thyroid-stimulating hormone) readily accessible High neutrophil-lymphocyte ratio, eosinophil/monocyte/lymphocyte counts; TSH troponins diagnosis drop white count lymphocyte can predict irAE. Other limited profiling. With fast-expanding approvals various types, knowledge help providers assess irAE-risk their patients. Prospective needed provide insight essential aspect therapy.

Language: Английский

Citations

206