Designing Cancer Immunotherapies That Engage T Cells and NK Cells

Annual Review of Immunology, Journal Year: 2022, Volume and Issue: 41(1), P. 17 - 38

Published: Nov. 29, 2022

T cells and natural killer (NK) have complementary roles in tumor immunity, dual cell NK attack thus offers opportunities to deepen the impact of immunotherapy. Recent work has also shown that play an important role recruiting dendritic tumors enhance induction CD8 responses, while IL-2 secreted by activates cells. Targeting immune evasion mechanisms from activating NKG2D receptor its MICA MICB ligands on for therapeutic intervention. Interestingly, share several inhibitory receptors can be targeted cell– cell–mediated immunity. These receptor-ligand systems include CD161-CLEC2D, TIGIT-CD155, NKG2A/CD94-HLA-E. We discuss emerging strategies based cytokines profoundly function both lymphocyte populations within tumors.

Language: Английский

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Deciphering cell lineage specification of human lung adenocarcinoma with single-cell RNA sequencing

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Nov. 11, 2021

Abstract Lung adenocarcinomas (LUAD) arise from precancerous lesions such as atypical adenomatous hyperplasia, which progress into adenocarcinoma in situ and minimally invasive adenocarcinoma, then finally adenocarcinoma. The cellular heterogeneity molecular events underlying this stepwise progression remain unclear. In study, we perform single-cell RNA sequencing of 268,471 cells collected 25 patients four histologic stages LUAD compare them to normal cell types. We detect a group closely resembling alveolar type 2 (AT2) that emerged during hyperplasia whose transcriptional profile began diverge AT2 progressed, taking on feature characteristic stem-like cells. identify genes related energy metabolism ribosome synthesis are upregulated early may promote progression. MDK TIMP1 could be potential biomarkers for understanding pathogenesis. Our work shed light the signatures distinct our findings facilitate diagnosis.

Language: Английский

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Chronic inflammation, cancer development and immunotherapy

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

Published: Oct. 14, 2022

Chronic inflammation plays a pivotal role in cancer development. Cancer cells interact with adjacent cellular components (pro-inflammatory cells, intrinsic immune stromal etc.) and non-cellular to form the inflammatory tumor microenvironment (TME). Interleukin 6 (IL-6), macrophage migration inhibitory factor (MIF), checkpoint factors other pro-inflammatory cytokines produced by TME are main mediators of intercellular communication TME, which link chronic stimulating different oncogenic signaling pathways improving escape promote In parallel, ability monocytes, T regulatory (Tregs) B (Bregs) perform homeostatic tolerogenic functions is hijacked leading local or systemic immunosuppression. Standard treatments for advanced malignancies such as chemotherapy radiotherapy have improved last decades. However, clinical outcomes certain malignant cancers not satisfactory due drug resistance side effects. The application therapy (ICT) has brought hope treatment, although therapeutic efficacy still limited immunosuppressive microenvironment. Emerging evidences reveal that ideal therapies including clearance disruption tumor-induced immunosuppression targeting suppressive well reactivation anti-tumor ICT. Here, we review impacts major their downstream molecules on We also discuss important management cancer.

Language: Английский

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Targeting oncogene and non-oncogene addiction to inflame the tumour microenvironment

Nature Reviews Drug Discovery, Journal Year: 2022, Volume and Issue: 21(6), P. 440 - 462

Published: March 15, 2022

Language: Английский

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Spatial omics: Navigating to the golden era of cancer research

Clinical and Translational Medicine, Journal Year: 2022, Volume and Issue: 12(1)

Published: Jan. 1, 2022

Abstract The idea that tumour microenvironment (TME) is organised in a spatial manner will not surprise many cancer biologists; however, systematically capturing architecture of TME still possible until recent decade. past five years have witnessed boom the research high‐throughput techniques and algorithms to delineate at an unprecedented level. Here, we review technological progress omics how advanced computation methods boost multi‐modal data analysis. Then, discussed potential clinical translations precision oncology, proposed transfer ecological principles biology interpretation. So far, placing us golden age research. Further development application may lead comprehensive decoding ecosystem bring current spatiotemporal molecular medical into entirely new paradigm.

Language: Английский

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Trial watch: Dendritic cell (DC)-based immunotherapy for cancer

OncoImmunology, Journal Year: 2022, Volume and Issue: 11(1)

Published: July 4, 2022

Dendritic cell (DC)-based vaccination for cancer treatment has seen considerable development over recent decades. However, this field is currently in a state of flux toward niche-applications, owing to paradigm-shifts immuno-oncology mobilized by T cell-targeting immunotherapies. DC vaccines are typically generated using autologous (patient-derived) DCs exposed tumor-associated or -specific antigens (TAAs TSAs), the presence immunostimulatory molecules induce maturation, followed reinfusion into patients. Accordingly, can TAA/TSA-specific CD8+/CD4+ responses. Yet, still shows suboptimal anti-tumor efficacy clinic. Extensive efforts ongoing improve immunogenicity and vaccines, often employing combinatorial chemo-immunotherapy regimens. In Trial Watch, we summarize preclinical clinical developments discuss trends future perspectives DC-based immunotherapy oncological indications.

Language: Английский

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Recent developments in application of single-cell RNA sequencing in the tumour immune microenvironment and cancer therapy

Military Medical Research, Journal Year: 2022, Volume and Issue: 9(1)

Published: Sept. 26, 2022

Abstract The advent of single-cell RNA sequencing (scRNA-seq) has provided insight into the tumour immune microenvironment (TIME). This review focuses on application scRNA-seq in investigation TIME. Over time, methods have evolved, and components TIME been deciphered with high resolution. In this review, we first introduced principle compared different approaches. Novel cell types TIME, a continuous transitional state, mutual intercommunication among present potential targets for prognosis prediction treatment cancer. Thus, concluded novel clusters cancer-associated fibroblasts (CAFs), T cells, tumour-associated macrophages (TAMs) dendritic cells (DCs) discovered after We also proposed development TAMs exhausted as well possible to interrupt process. addition, therapeutic interventions based cellular interactions were summarized. For decades, quantification adopted clinical practice predict patient survival response therapy is expected play an important role precise Summarizing current findings, believe that advances technology wide analysis can lead discovery perspectives cancer therapy, which subsequently be implemented clinic. Finally, propose some future directions field studies aided by technology.

Language: Английский

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Targeting immunogenic cell stress and death for cancer therapy

Nature Reviews Drug Discovery, Journal Year: 2024, Volume and Issue: 23(6), P. 445 - 460

Published: April 15, 2024

Language: Английский

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Artificial intelligence for digital and computational pathology

Nature Reviews Bioengineering, Journal Year: 2023, Volume and Issue: 1(12), P. 930 - 949

Published: Oct. 2, 2023

Language: Английский

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Yeast-derived nanoparticles remodel the immunosuppressive microenvironment in tumor and tumor-draining lymph nodes to suppress tumor growth

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Jan. 10, 2022

Abstract Microbe-based cancer immunotherapy has recently emerged as a hot topic for treatment. However, serious limitations remain including infection associated side-effect and unsatisfactory outcomes in clinic trials. Here, we fabricate different sizes of nano-formulations derived from yeast cell wall (YCW NPs) by differential centrifugation. The induction anticancer immunity our formulations appears to inversely correlate with their size due the ability accumulate tumor-draining lymph node (TDLN). Moreover, use percolation model explain distribution behavior toward TDLN. abundance functional orientation each effector component are significantly improved not only microenvironment tumor but also TDLN following small YCW NPs In combination programmed death-ligand 1 (PD-L1) blockade, demonstrate efficiency melanoma-challenged mice. We delineate potential strategy target immunosuppressive microbe-based nanoparticles highlight role effect immune therapeutics.

Language: Английский

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