FOXP3+ regulatory T cells and the immune escape in solid tumours DOI Creative Commons
Yiran Qiu,

Shouyu Ke,

Jieqiong Chen

et al.

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

Published: Oct. 13, 2022

FOXP3+ regulatory T (Treg) cells play critical roles in establishing the immunosuppressive tumour microenvironment, which is achieved and dynamically maintained with contribution of various stromal immune cell subsets. However, dynamics non-lymphoid Treg mutual regulation other types solid microenvironment remains largely unclear. In this review, we summarize latest findings on dynamic connections reciprocal regulations subsets accordance well-established new emerging hallmarks cancer, especially escape tumours. Our comprehension interplay between key cancer may provide insights into development next-generation engineered cell-based treatments for

Language: Английский

Stem-like exhausted and memory CD8+ T cells in cancer DOI
Thomas Gebhardt, Simone L. Park, Ian A. Parish

et al.

Nature reviews. Cancer, Journal Year: 2023, Volume and Issue: 23(11), P. 780 - 798

Published: Oct. 11, 2023

Language: Английский

Citations

73
MultiNicheNet: a flexible framework for differential cell-cell communication analysis from multi-sample multi-condition single-cell transcriptomics data DOI Creative Commons
Robin Browaeys, Jeroen Gilis, Chananchida Sang-aram

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: June 14, 2023

Abstract Dysregulated cell-cell communication is a hallmark of many disease phenotypes. Due to recent advances in single-cell transcriptomics and computational approaches, it now possible study intercellular on genome- tissue-wide scale. However, most current inference tools have limitations when analyzing data from multiple samples conditions. Their main limitation that they do not address inter-sample heterogeneity adequately, which could lead false inference. This issue crucial for human cohort scRNA-seq datasets, complicating the comparison between healthy diseased subjects. Therefore, we developed MultiNicheNet ( https://github.com/saeyslab/multinichenetr ), novel framework better analyze multi-sample multi-condition data. The goals are inferring differentially expressed active ligand-receptor pairs conditions interest predicting putative downstream target genes these pairs. To achieve this goal, applies principles state-of-the-art differential expression algorithms As result, users can while adequately addressing heterogeneity, handling complex multifactorial experimental designs, correcting batch effects covariates. Moreover, uses NicheNet-v2, our new substantially improved version NicheNet’s network ligand-target prior knowledge model. We applied patient several diseases (breast cancer, squamous cell carcinoma, multisystem inflammatory syndrome children, lung fibrosis). For diseases, uncovered known aberrant signaling processes. also demonstrated MultiNicheNet’s potential perform non-trivial analysis tasks, such as studying between- within-group differences dynamics response therapy. final example, used MulitNicheNet elucidate dysregulated idiopathic pulmonary fibrosis integrated atlas Given anticipated increase datasets due technological advancements extensive atlas-building integration efforts, expect will be valuable tool uncover states.

Language: Английский

Citations

69
A DNA/DMXAA/Metal–Organic Framework Activator of Innate Immunity for Boosting Anticancer Immunity DOI
Xiaojing Chen,

Qianyun Tang,

Jinqiang Wang

et al.

Advanced Materials, Journal Year: 2023, Volume and Issue: unknown, P. 2210440 - 2210440

Published: Jan. 19, 2023

Immunotherapy has achieved revolutionary success in clinics, but it remains challenging for treating hepatocellular carcinoma (HCC) characterized by high vascularization. Here, is reported that metal-organic framework-801 (MOF-801) can be employed as a stimulator of interferon genes (STING) through Toll-like receptor 4 (TLR4) not just drug delivery carrier. Notably, cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODNs) and 5, 6-dimethylxanthenone-4-acetic acid (DMXAA) STING agonist with vascular disrupting function coordinates MOF-801 to self-assemble into nanoparticle (MOF-CpG-DMXAA) effectively delivers CpG ODNs DMXAA cells synergistically improving the tumor microenvironment reprogramming tumor-associated macrophages (TAMs), promoting dendritic (DCs) maturation, well destroying blood vessels. In HCC-bearing mouse models, demonstrated MOF-CpG-DMXAA triggers systemic immune activation stimulates robust tumoricidal immunity, resulting superior immunotherapeutic efficiency orthotopic recurrent HCC.

Language: Английский

Citations

50
Mature dendritic cells enriched in immunoregulatory molecules (mregDCs): A novel population in the tumour microenvironment and immunotherapy target DOI Creative Commons
Jiaxin Li, Jun Zhou, Huanhuan Huang

et al.

Clinical and Translational Medicine, Journal Year: 2023, Volume and Issue: 13(2)

Published: Feb. 1, 2023

Abstract Background Dendritic cells (DCs) mediate divergent immune effects by activating T or negatively regulating the response to promote tolerance. They perform specific functions determined their tissue distribution and maturation state. Traditionally, immature semimature DCs were described have immunosuppressive effects, leading Nonetheless, recent research has demonstrated that mature can also suppress under certain circumstances. Main body Mature enriched in immunoregulatory molecules (mregDCs) emerged as a regulatory module across species tumour types. Indeed, distinct roles of mregDCs immunotherapy sparked interest researchers field single‐cell omics. In particular, these found be associated with positive favourable prognosis. Conclusion Here, we provide general overview latest most notable advances findings regarding basic features complex nonmalignant diseases microenvironment. We emphasise important clinical implications tumours.

Language: Английский

Citations

48
Cancer organoids 2.0: modelling the complexity of the tumour immune microenvironment DOI
Roel Polak, Elisa Zhang, Calvin J. Kuo

et al.

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: 24(8), P. 523 - 539

Published: July 8, 2024

Language: Английский

Citations

48
Regulatory T cell-mediated immunosuppression orchestrated by cancer: towards an immuno-genomic paradigm for precision medicine DOI
Shogo Kumagai, Kota Itahashi, Hiroyoshi Nishikawa

et al.

Nature Reviews Clinical Oncology, Journal Year: 2024, Volume and Issue: 21(5), P. 337 - 353

Published: Feb. 29, 2024

Language: Английский

Citations

43
Single cell deciphering of progression trajectories of the tumor ecosystem in head and neck cancer DOI Creative Commons
Zhanli Liu,

Xiangyan Meng,

Rujuan Bao

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 22, 2024

Abstract Head and neck squamous cell carcinoma is the sixth most common cancer worldwide has high heterogeneity unsatisfactory outcomes. To better characterize tumor progression trajectory, we perform single-cell RNA sequencing of normal tissue, precancerous early-stage, advanced-stage lymph node, recurrent tumors tissue samples. We identify transcriptional development trajectory malignant epithelial cells a tumorigenic subcluster regulated by TFDP1 . Furthermore, find that infiltration POSTN + fibroblasts SPP1 macrophages gradually increases with progression; their interaction or also increase to shape desmoplastic microenvironment reprogram promote progression. Additionally, demonstrate during node metastasis, exhausted CD8 T CXCL13 expression strongly interact acquire more aggressive phenotypes extranodal expansion. Finally, delineate distinct features in primary tumors, providing theoretical foundation for precise selection targeted therapy at different stages. In summary, current study offers comprehensive landscape deep insight into microenvironmental reprogramming throughout initiation, progression, metastasis recurrence head carcinoma.

Language: Английский

Citations

24
IL-23 stabilizes an effector Treg cell program in the tumor microenvironment DOI Creative Commons
Tobias Wertheimer, Pascale Zwicky, Lukas Rindlisbacher

et al.

Nature Immunology, Journal Year: 2024, Volume and Issue: 25(3), P. 512 - 524

Published: Feb. 14, 2024

Abstract Interleukin-23 (IL-23) is a proinflammatory cytokine mainly produced by myeloid cells that promotes tumor growth in various preclinical cancer models and correlates with adverse outcomes. However, as to how IL-23 fuels unclear. Here, we found tumor-associated macrophages be the main source of mouse human microenvironments. Among IL-23-sensing cells, identified subset tumor-infiltrating regulatory T (T reg ) display highly suppressive phenotype across tumors. The use three solid combination genetic ablation Il23r revealed they are responsible for tumor-promoting effect IL-23. Mechanistically, sensing represents crucial signal driving maintenance stabilization effector involving transcription factor Foxp3. Our data support targeting IL-23/IL-23R axis may represent means eliciting antitumor immunity.

Language: Английский

Citations

19
OMIP‐102: 50‐color phenotyping of the human immune system with in‐depth assessment of T cells and dendritic cells DOI Creative Commons
A Konecny, Peter L. Mage, Aaron J. Tyznik

et al.

Cytometry Part A, Journal Year: 2024, Volume and Issue: 105(6), P. 430 - 436

Published: April 18, 2024

Abstract We report the development of an optimized 50‐color spectral flow cytometry panel designed for in‐depth analysis immune system in human blood and tissues, with goal maximizing amount information that can be collected using currently available platforms. established tested this peripheral mononuclear cells (PBMCs), but included CD45 to enable its future use tissue samples. The contains lineage markers all major cell subsets, extensive set phenotyping focused on activation differentiation status T dendritic (DC) compartment. outline biological insight gained from simultaneous measurement such a large number proteins propose approach provides unique opportunity comprehensive exploration samples limited cells. Of note, we compatible sorting further downstream applications. Furthermore, facilitate wide‐spread implementation across different cohorts samples, trimmed‐down 45‐color version which used Finally, generate panel, utilized not only existing design guidelines, also developed new metrics systematically identify optimal combination 50 fluorochromes evaluate fluorochrome‐specific resolution context unmixing matrix.

Language: Английский

Citations

19
Mn2+/CpG Oligodeoxynucleotides Codecorated Black Phosphorus Nanosheet Platform for Enhanced Antitumor Potency in Multimodal Therapy DOI
Kai Ling, Jintao Zheng, Xiaohong Jiang

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(4), P. 2841 - 2860

Published: Jan. 22, 2024

Manganese ions (Mn2+)-coordinated nanoparticles have emerged as a promising class of antitumor nanotherapeutics, capable simultaneously disrupting the immunosuppressive tumor microenvironment (TME) and triggering stimulator interferon genes (STING) pathway-dependent immunity. However, activation STING signaling by Mn2+-based monotherapies is suboptimal for comprehensive stimulation antigen presenting cells reversal immunosuppression in TME. Here, we report design Mn2+/CpG oligodeoxynucleotides (ODNs) codecorated black phosphorus nanosheet (BPNS@Mn2+/CpG) platform based on Mn2+ modification BPNS subsequent adsorption synthetic CpG ODNs. The coordination significantly improved stability acidic TME endosomal compartments can disrupt coordination, pH-responsive release ODNs to effectively activate Toll-like receptor 9 pathways. As result, M2-type macrophages immature dendritic were strongly stimulated TME, thereby increasing T lymphocyte infiltration reversing within Phototherapy chemodynamic therapy, utilizing BPNS@Mn2+/CpG platform, demonstrated efficacy inducing immunogenic cell death upon 808 nm laser irradiation. Importantly, treatment with irradiation exhibited significant therapeutic against irradiated primary suppressed growth nonirradiated distant tumor. Moreover, it induced robust immune memory, providing long-lasting protection recurrence. This study enhanced potency multimodal its proof-of-concept application metal ion-modified material effective DNA/drug delivery immunotherapy.

Language: Английский

Citations

18