Emerging phagocytosis checkpoints in cancer immunotherapy

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

Published: March 7, 2023

Abstract Cancer immunotherapy, mainly including immune checkpoints-targeted therapy and the adoptive transfer of engineered cells, has revolutionized oncology landscape as it utilizes patients’ own systems in combating cancer cells. cells escape surveillance by hijacking corresponding inhibitory pathways via overexpressing checkpoint genes. Phagocytosis checkpoints, such CD47, CD24, MHC-I, PD-L1, STC-1 GD2, have emerged essential checkpoints for immunotherapy functioning “don’t eat me” signals or interacting with “eat to suppress responses. link innate immunity adaptive immunotherapy. Genetic ablation these phagocytosis well blockade their signaling pathways, robustly augments reduces tumor size. Among all CD47 is most thoroughly studied a rising star among targets treatment. CD47-targeting antibodies inhibitors been investigated various preclinical clinical trials. However, anemia thrombocytopenia appear be formidable challenges since ubiquitously expressed on erythrocytes. Here, we review reported discussing mechanisms functions highlight progress targeting discuss potential solutions smooth way combination immunotherapeutic strategies that involve both

Language: Английский

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The pre-existing T cell landscape determines the response to bispecific T cell engagers in multiple myeloma patients

Cancer Cell, Journal Year: 2023, Volume and Issue: 41(4), P. 711 - 725.e6

Published: March 9, 2023

Bispecific T cell engagers (TCEs) have shown promise in the treatment of various cancers, but immunological mechanism and molecular determinants primary acquired resistance to TCEs remain poorly understood. Here, we identify conserved behaviors bone marrow-residing cells multiple myeloma patients undergoing BCMAxCD3 TCE therapy. We show that immune repertoire reacts therapy with state-dependent clonal expansion find evidence supporting coupling tumor recognition via major histocompatibility complex class I (MHC I), exhaustion, clinical response. abundance exhausted-like CD8+ clones be associated response failure, describe loss target epitope MHC as tumor-intrinsic adaptations TCEs. These findings advance our understanding vivo humans provide rationale for predictive immune-monitoring conditioning guide future immunotherapy hematological malignancies.

Language: Английский

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Functional states of myeloid cells in cancer

Cancer Cell, Journal Year: 2023, Volume and Issue: 41(3), P. 490 - 504

Published: March 1, 2023

Language: Английский

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Combination cancer immunotherapies: Emerging treatment strategies adapted to the tumor microenvironment

Science Translational Medicine, Journal Year: 2022, Volume and Issue: 14(670)

Published: Nov. 9, 2022

Immune checkpoint blockade (ICB) has revolutionized cancer treatment. However, resistance to ICB occurs frequently due tumor-intrinsic alterations or extrinsic factors in the tumor microenvironment. This Viewpoint aims give an update on recent developments immunotherapy for solid tumors and highlights progress translational research clinical practice.

Language: Английский

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NK cells and solid tumors: therapeutic potential and persisting obstacles

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

Published: Nov. 1, 2022

Abstract Natural killer (NK) cells, which are innate lymphocytes endowed with potent cytotoxic activity, have recently attracted attention as potential anticancer therapeutics. While NK cells mediate encouraging responses in patients leukemia, the therapeutic effects of cell infusion solid tumors limited. Preclinical and clinical data suggest that efficacy against malignancies is hampered by several factors including inadequate tumor infiltration persistence/activation microenvironment (TME). A number metabolic features TME hypoxia well elevated levels adenosine, reactive oxygen species, prostaglandins negatively affect activity. Moreover, cancer-associated fibroblasts, tumor-associated macrophages, myeloid-derived suppressor regulatory T actively suppress cell-dependent immunity. Here, we review cellular barriers inhibit neoplasms discuss strategies to circumvent such obstacles towards superior

Language: Английский

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Targeting macrophages in hematological malignancies: recent advances and future directions

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

Published: Aug. 17, 2022

Abstract Emerging evidence indicates that the detection and clearance of cancer cells via phagocytosis induced by innate immune checkpoints play significant roles in tumor-mediated escape. The most well-described are “don’t eat me” signals, including CD47/signal regulatory protein α axis (SIRPα), PD-1/PD-L1 axis, CD24/SIGLEC-10 MHC-I/LILRB1 axis. Molecules have been developed to block these pathways enhance phagocytic activity against tumors. Several clinical studies investigated safety efficacy CD47 blockades, either alone or combination with existing therapy hematological malignancies, myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), lymphoma. However, only a minority patients responses treatments alone. Combining blockades other treatment modalities studies, early results suggesting synergistic therapeutic effect. Targeting macrophages bispecific antibodies being explored blood therapy. Furthermore, reprogramming pro-tumor anti-tumor macrophages, CAR (CAR-M) demonstrate activities. In this review, we elucidated distinct types macrophage-targeted strategies from preclinical experiments trials, outlined potential approaches developed.

Language: Английский

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How chemokines organize the tumour microenvironment

Nature reviews. Cancer, Journal Year: 2023, Volume and Issue: 24(1), P. 28 - 50

Published: Dec. 8, 2023

Language: Английский

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CSF1R inhibitors are emerging immunotherapeutic drugs for cancer treatment

European Journal of Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 245, P. 114884 - 114884

Published: Oct. 30, 2022

Language: Английский

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Advances in single-cell RNA sequencing and its applications in cancer research

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

Published: Aug. 24, 2023

Abstract Cancers are a group of heterogeneous diseases characterized by the acquisition functional capabilities during transition from normal to neoplastic state. Powerful experimental and computational tools can be applied elucidate mechanisms occurrence, progression, metastasis, drug resistance; however, challenges remain. Bulk RNA sequencing techniques only reflect average gene expression in sample, making it difficult understand tumor heterogeneity microenvironment. The emergence development single-cell (scRNA-seq) technologies have provided opportunities subtle changes biology identifying distinct cell subpopulations, dissecting microenvironment, characterizing cellular genomic mutations. Recently, scRNA-seq technology has been increasingly used cancer studies explore which increased understanding tumorigenesis evolution. This review summarizes basic processes their increasing applications research clinical practice.

Language: Английский

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Controlling the biodistribution and clearance of nanomedicines

Nature Reviews Bioengineering, Journal Year: 2023, Volume and Issue: 2(3), P. 214 - 232

Published: Dec. 20, 2023

Language: Английский

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