Single-Cell Transcriptomics Reveals the Complexity of the Tumor Microenvironment of Treatment-Naive Osteosarcoma DOI Creative Commons
Yun Liu, Wenyu Feng, Yan Dai

et al.

Frontiers in Oncology, Journal Year: 2021, Volume and Issue: 11

Published: July 21, 2021

Osteosarcoma (OS), which occurs most commonly in adolescents, is associated with a high degree of malignancy and poor prognosis. In order to develop an accurate treatment for OS, deeper understanding its complex tumor microenvironment (TME) required. the present study, tissues were isolated from six patients then subjected single-cell RNA sequencing (scRNA-seq) using 10× Genomics platform. Multiplex immunofluorescence staining was subsequently used validate subsets identified by scRNA-seq. ScRNA-seq OS performed prior neoadjuvant chemotherapy, data obtained on 29,278 cells. A total nine major cell types identified, transcriptional map revealed. Identified osteoblastic cells divided into five subsets, those significant prognostic correlation determined deconvolution algorithm. Thereby, different transcription patterns cellular subtypes reported, key factors survival prognosis identified. Furthermore, regulation osteolysis via receptor activator nuclear factor kappa-B ligand role regulating angiogenesis through vascular endothelial growth factor-A C3_TXNIP+ macrophages C5_IFIT1+ found regulate regulatory T participate CD8+ exhaustion, illustrating possibility immunotherapy that could target macrophages. Our findings here show C1_osteoblastic promote angiogenesis, this addition, depletion important feature OS. More importantly, study provided valuable resource in-depth heterogeneity TME.

Language: Английский

Therapeutic Targeting of the Tumor Microenvironment DOI Open Access
Leire Bejarano, Marta Joana Costa Jordão, Johanna A. Joyce

et al.

Cancer Discovery, Journal Year: 2021, Volume and Issue: 11(4), P. 933 - 959

Published: April 1, 2021

Abstract Strategies to therapeutically target the tumor microenvironment (TME) have emerged as a promising approach for cancer treatment in recent years due critical roles of TME regulating progression and modulating response standard-of-care therapies. Here, we summarize current knowledge regarding most advanced TME-directed therapies, which either been clinically approved or are currently being evaluated trials, including immunotherapies, antiangiogenic drugs, treatments directed against cancer-associated fibroblasts extracellular matrix. We also discuss some challenges associated with future perspectives this evolving field. Significance: This review provides comprehensive analysis therapies targeting TME, combining discussion underlying basic biology clinical evaluation different therapeutic approaches, highlighting perspectives.

Language: Английский

Citations

1093
Pan-cancer single-cell landscape of tumor-infiltrating T cells DOI
Liangtao Zheng, Shishang Qin, Wen Si

et al.

Science, Journal Year: 2021, Volume and Issue: 374(6574)

Published: Dec. 16, 2021

T cells play a central role in cancer immunotherapy, but we lack systematic comparison of the heterogeneity and dynamics tumor-infiltrating across types. We built single-cell RNA-sequencing pan-cancer atlas for 316 donors 21 types revealed distinct cell composition patterns. found multiple state-transition paths exhaustion CD8+ preference those among different tumor Certain populations showed specific correlation with patient properties such as mutation burden, shedding light on possible determinants microenvironment. compositions within tumors alone could classify patients into groups clinical trait specificity, providing new insights immunity precision immunotherapy targeting cells.

Language: Английский

Citations

860
A single-cell map of intratumoral changes during anti-PD1 treatment of patients with breast cancer DOI
Ayse Bassez, Hanne Vos, Laurien Van Dyck

et al.

Nature Medicine, Journal Year: 2021, Volume and Issue: 27(5), P. 820 - 832

Published: May 1, 2021

Language: Английский

Citations

553
Effect of the intratumoral microbiota on spatial and cellular heterogeneity in cancer DOI Creative Commons
Jorge Luis Galeano Niño, Hanrui Wu, Kaitlyn D. LaCourse

et al.

Nature, Journal Year: 2022, Volume and Issue: 611(7937), P. 810 - 817

Published: Nov. 16, 2022

Abstract The tumour-associated microbiota is an intrinsic component of the tumour microenvironment across human cancer types 1,2 . Intratumoral host–microbiota studies have so far largely relied on bulk tissue analysis 1–3 , which obscures spatial distribution and localized effect within tumours. Here, by applying in situ spatial-profiling technologies 4 single-cell RNA sequencing 5 to oral squamous cell carcinoma colorectal cancer, we reveal spatial, cellular molecular host–microbe interactions. We adapted 10x Visium transcriptomics determine identity location intratumoral microbial communities patient tissues. Using GeoMx digital profiling 6 show that bacterial populate microniches are less vascularized, highly immuno‑suppressive associated with malignant cells lower levels Ki-67 as compared bacteria-negative regions. developed a RNA-sequencing method name INVADEseq (invasion–adhesion-directed expression sequencing) and, this tumours, identify cell-associated bacteria host they interact, well uncovering alterations transcriptional pathways involved inflammation, metastasis, dormancy DNA repair. Through functional studies, infected invade their surrounding environment single recruit myeloid Collectively, our data not random; instead, it organized immune epithelial functions promote progression.

Language: Английский

Citations

468
Discriminating mild from critical COVID-19 by innate and adaptive immune single-cell profiling of bronchoalveolar lavages DOI Creative Commons
Els Wauters, Pierre Van Mol, Abhishek D. Garg

et al.

Cell Research, Journal Year: 2021, Volume and Issue: 31(3), P. 272 - 290

Published: Jan. 21, 2021

Abstract How the innate and adaptive host immune system miscommunicate to worsen COVID-19 immunopathology has not been fully elucidated. Here, we perform single-cell deep-immune profiling of bronchoalveolar lavage (BAL) samples from 5 patients with mild 26 critical in comparison BALs non-COVID-19 pneumonia normal lung. We use pseudotime inference build T-cell monocyte-to-macrophage trajectories model gene expression changes along them. In COVID-19, CD8 + resident-memory (T RM ) CD4 T-helper-17 H17 cells undergo active (presumably antigen-driven) expansion towards end trajectory, are characterized by good effector functions, while they remain more naïve. Vice versa, T-cells T-helper-1 characteristics H1 -like) expressing exhaustion markers EX enriched halfway their where also exhibit show evidence inflammation-associated stress at trajectories. Monocyte-to-macrophage that chronic hyperinflammatory monocytes alveolar macrophages, otherwise anti-inflammatory antigen-presenting characteristics, depleted. contribute an ATP-purinergic signaling-inflammasome footprint could enable associated fibrosis disease-severity. Finally, viral RNA-tracking reveals infected lung epithelial cells, a significant proportion neutrophils macrophages involved clearance.

Language: Английский

Citations

330
Next-generation cancer organoids DOI
Bauer L. LeSavage, Riley A. Suhar, Nicolas Broguière

et al.

Nature Materials, Journal Year: 2021, Volume and Issue: 21(2), P. 143 - 159

Published: Aug. 12, 2021

Language: Английский

Citations

321
Tumour-infiltrating B cells: immunological mechanisms, clinical impact and therapeutic opportunities DOI
Céline M. Laumont, Allyson C. Banville, Mara Gilardi

et al.

Nature reviews. Cancer, Journal Year: 2022, Volume and Issue: 22(7), P. 414 - 430

Published: April 7, 2022

Language: Английский

Citations

320
CXCR6 positions cytotoxic T cells to receive critical survival signals in the tumor microenvironment DOI Creative Commons
Mauro Di Pilato, Raphael Kfuri-Rubens, Jasper N. Pruessmann

et al.

Cell, Journal Year: 2021, Volume and Issue: 184(17), P. 4512 - 4530.e22

Published: Aug. 1, 2021

Language: Английский

Citations

318
A single‐cell RNA expression atlas of normal, preneoplastic and tumorigenic states in the human breast DOI Creative Commons
Bhupinder Pal, Yunshun Chen, François Vaillant

et al.

The EMBO Journal, Journal Year: 2021, Volume and Issue: 40(11)

Published: May 5, 2021

To examine global changes in breast heterogeneity across different states, we determined the single-cell transcriptomes of > 340,000 cells encompassing normal breast, preneoplastic BRCA1

Language: Английский

Citations

316
Pan-cancer single-cell analysis reveals the heterogeneity and plasticity of cancer-associated fibroblasts in the tumor microenvironment DOI Creative Commons
Han Luo, Xuyang Xia, Li‐Bin Huang

et al.

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

Published: Nov. 4, 2022

Abstract Cancer-associated fibroblasts (CAFs) are the predominant components of tumor microenvironment (TME) and influence cancer hallmarks, but without systematic investigation on their ubiquitous characteristics across different types. Here, we perform pan-cancer analysis 226 samples 10 solid types to profile TME at single-cell resolution, illustrating commonalities/plasticity heterogenous CAFs. Activation trajectory major CAF is divided into three states, exhibiting distinct interactions with other cell components, relating prognosis immunotherapy. Moreover, minor represent alternative origin from (e.g., endothelia macrophages). Particularly, presentation endothelial-to-mesenchymal transition CAF, which may interact proximal SPP 1 + tumor-associated macrophages, implicated in survival stratifications. Our study comprehensively profiles shared dynamics CAFs, highlight heterogeneity plasticity Browser integrated information available https://gist-fgl.github.io/sc-caf-atlas/ .

Language: Английский

Citations

296