Spatially confined sub-tumor microenvironments in pancreatic cancer

Cell, Journal Year: 2021, Volume and Issue: 184(22), P. 5577 - 5592.e18

Published: Oct. 1, 2021

Intratumoral heterogeneity is a critical frontier in understanding how the tumor microenvironment (TME) propels malignant progression. Here, we deconvolute human pancreatic TME through large-scale integration of histology-guided regional multiOMICs with clinical data and patient-derived preclinical models. We discover "subTMEs," histologically definable tissue states anchored fibroblast plasticity, relationships to immunity, subtypes, differentiation, treatment response. "Reactive" subTMEs rich complex but functionally coordinated communities were immune hot inhabited by aggressive cell phenotypes. The matrix-rich "deserted" harbored fewer activated fibroblasts tumor-suppressive features yet markedly chemoprotective enriched upon chemotherapy. SubTMEs originated differentiation trajectories, transitory notable both single-cell transcriptomics situ. intratumoral co-occurrence produced patient-specific phenotypic computationally predictable tightly linked biology. Therefore, within plentiful, notorious not random marks fundamental organizational units.

Language: Английский

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Single-cell atlas of tumor cell evolution in response to therapy in hepatocellular carcinoma and intrahepatic cholangiocarcinoma

Journal of Hepatology, Journal Year: 2021, Volume and Issue: 75(6), P. 1397 - 1408

Published: June 30, 2021

Language: Английский

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Emerging evidence for adapting radiotherapy to immunotherapy

Nature Reviews Clinical Oncology, Journal Year: 2023, Volume and Issue: 20(8), P. 543 - 557

Published: June 6, 2023

Language: Английский

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ATP and cancer immunosurveillance

The EMBO Journal, Journal Year: 2021, Volume and Issue: 40(13)

Published: June 14, 2021

Language: Английский

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Tumor heterogeneity reshapes the tumor microenvironment to influence drug resistance

International Journal of Biological Sciences, Journal Year: 2022, Volume and Issue: 18(7), P. 3019 - 3033

Published: Jan. 1, 2022

Tumor heterogeneity is one of the hallmarks cancer and a challenge in field oncology.Tumor main cause drug resistance, leading to therapeutic failure.Mechanically, tumor either directly affects targets or shapes microenvironment (TME) by defining transcriptomic phenotypic profiles influence resistance.Tumor evolves spatially temporally during development, constant reprogramming TME.Advances molecular profiling technologies precision oncology platforms have allowed us uncover impact on resistance context TME.In this review, we focus processes which genomic mutations drive mechanisms through reprograms TME affect patient prognosis.

Language: Английский

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PHGDH heterogeneity potentiates cancer cell dissemination and metastasis

Nature, Journal Year: 2022, Volume and Issue: 605(7911), P. 747 - 753

Published: May 18, 2022

Language: Английский

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Radiotherapy as a tool to elicit clinically actionable signalling pathways in cancer

Nature Reviews Clinical Oncology, Journal Year: 2021, Volume and Issue: 19(2), P. 114 - 131

Published: Nov. 24, 2021

Language: Английский

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Thermal immuno-nanomedicine in cancer

Nature Reviews Clinical Oncology, Journal Year: 2023, Volume and Issue: 20(2), P. 116 - 134

Published: Jan. 5, 2023

Language: Английский

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Exosomes in the hypoxic TME: from release, uptake and biofunctions to clinical applications

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

Published: Jan. 17, 2022

Abstract Hypoxia is a remarkable trait of the tumor microenvironment (TME). When facing selective pressure, cells show various adaptive characteristics, such as changes in expression cancer hallmarks (increased proliferation, suppressed apoptosis, immune evasion, and so on) more frequent cell communication. Because adaptation to hypoxia, exploring association between communication mediators hypoxia has become increasingly important. Exosomes are important information carriers cell-to-cell Abundant evidence proven that effects TME mediated by exosomes, with occasional formation feedback loops. In this review, we equally focus on biogenesis heterogeneity cancer-derived exosomes their functions under describe known potential mechanism ascribed hypoxia. Notably, call attention size change hypoxic cell-derived characteristic long neglected, propose some possible change. Finally, jointly considering recent developments understanding tumors, noteworthy problems field urgently need be solved for better research clinical application.

Language: Английский

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Early Tumor–Immune Microenvironmental Remodeling and Response to First-Line Fluoropyrimidine and Platinum Chemotherapy in Advanced Gastric Cancer

Cancer Discovery, Journal Year: 2021, Volume and Issue: 12(4), P. 984 - 1001

Published: Dec. 21, 2021

Chemotherapy is ubiquitous in first-line treatment of advanced gastric cancer, yet responses are heterogeneous, and little known about mediators chemotherapy response. To move forward, an understanding the effects standard on tumor-immune microenvironment (TME) needed. Coupling whole-exome sequencing, bulk RNA single-cell transcriptomics from paired pretreatment on-treatment samples treatment-naïve patients with HER2-positive HER2-negative we define features associated response to platinum-based chemotherapy. Response was TME remodeling including natural killer (NK) cell recruitment, decreased tumor-associated macrophages, M1-macrophage repolarization, increased effector T-cell infiltration. Among nonresponders, observed low/absent PD-L1 expression or modulation, increases Wnt signaling, B-cell infiltration, LAG3-expressing T cells coupled exodus dendritic cells. We did not observe significant genomic changes early sampling. provide a map modulation nominate candidate future approaches. Using during chemotherapy, identify chemotherapy-induced NK-cell macrophage antigen presentation among responders. Increased LAG3 abundance were seen emphasizing resistance. This article highlighted In Issue feature, p. 873.

Language: Английский

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