CAF-macrophage crosstalk in tumour microenvironments governs the response to immune checkpoint blockade in gastric cancer peritoneal metastases DOI Creative Commons
Yuanfang Li, Yongqiang Zheng,

Jiaqian Huang

и другие.

Gut, Год журнала: 2024, Номер unknown, С. gutjnl - 333617

Опубликована: Ноя. 12, 2024

Background Peritoneal metastasis is the most common pattern of gastric cancer. Patients with cancer peritoneal (GCPM) have a poor prognosis and respond poorly to conventional treatments. Recently, immune checkpoint blockade (ICB) has demonstrated favourable efficacy in treatment GCPM. Stratification best responders elucidation resistance mechanisms ICB therapies are highly important remain major clinical challenges. Design We performed phase II trial involving patients GCPM treated (sintilimab) combined chemotherapy. The samples primary tumours, GCPMs peripheral blood from were collected for single-cell sequencing comprehensively interpret tumour microenvironment its impacts on immunotherapy efficacy. Results ecosystem coordinates unique immunosuppressive distinct that GC, which dominated by stroma-myeloid niche composed SPP1+tumour-associated macrophages (TAMs) Thrombospondin 2 (THBS2)+matrix cancer-associated fibroblasts (mCAFs). Consequently, this crosstalk mediator Mechanistically, accumulated THBS2+mCAFs facilitate recruitment peritoneum-specific tissue-resident their transformation into SPP1+TAMs via complement C3 receptor C3a 1 (C3AR1), thereby forming protumoral niche. Blocking C3-C3AR1 axis disrupts significantly improves benefits vivo models. Conclusion Our findings provide new molecular portrait cell compositions associated aid prioritisation therapeutic candidates potentiate immunotherapy.

Язык: Английский

IL-1β+ macrophages fuel pathogenic inflammation in pancreatic cancer DOI
Nicoletta Caronni, Federica La Terza,

Francesco Maria Vittoria

и другие.

Nature, Год журнала: 2023, Номер 623(7986), С. 415 - 422

Опубликована: Ноя. 1, 2023

Язык: Английский

Процитировано

150
How chemokines organize the tumour microenvironment DOI
Thorsten R. Mempel, Julia K. Lill, Lukas M. Altenburger

и другие.

Nature reviews. Cancer, Год журнала: 2023, Номер 24(1), С. 28 - 50

Опубликована: Дек. 8, 2023

Язык: Английский

Процитировано

103
Spatial and Temporal Mapping of Breast Cancer Lung Metastases Identify TREM2 Macrophages as Regulators of the Metastatic Boundary DOI
Ido Yofe, Tamar Shami, Noam Cohen

и другие.

Cancer Discovery, Год журнала: 2023, Номер 13(12), С. 2610 - 2631

Опубликована: Сен. 27, 2023

Abstract Cancer mortality primarily stems from metastatic recurrence, emphasizing the urgent need for developing effective metastasis-targeted immunotherapies. To better understand cellular and molecular events shaping niches, we used a spontaneous breast cancer lung metastasis model to create single-cell atlas spanning different stages regions. We found that premetastatic lungs are infiltrated by inflammatory neutrophils monocytes, followed accumulation of suppressive macrophages with emergence metastases. Spatial profiling revealed metastasis-associated immune cells were present in core, exception TREM2+ regulatory uniquely enriched at invasive margin, consistent across both murine models human patient samples. These (Mreg) contribute formation an immune-suppressive niche, cloaking tumor surveillance. Our study provides compendium cell dynamics informing development metastasis-targeting Significance: Temporal spatial analysis new players modulating surveillance suppression. highlights distinct populations TREM2 as modulators microenvironment metastasis, key determinant defining pointing myeloid checkpoints improve therapeutic strategies. This article is featured Selected Articles Issue, p. 2489

Язык: Английский

Процитировано

47
Extracellular vesicles remodel tumor environment for cancer immunotherapy DOI Creative Commons
Yue Ming,

Shengyun Hu,

Haifeng Sun

и другие.

Molecular Cancer, Год журнала: 2023, Номер 22(1)

Опубликована: Дек. 13, 2023

Tumor immunotherapy has transformed neoplastic disease management, yet low response rates and immune complications persist as major challenges. Extracellular vesicles including exosomes have emerged therapeutic agents actively involved in a diverse range of pathological conditions. Mounting evidence suggests that alterations the quantity composition extracellular (EVs) contribute to remodeling immune-suppressive tumor microenvironment (TME), thereby influencing efficacy immunotherapy. This revelation sparked clinical interest utilizing EVs for sensitization. In this perspective article, we present comprehensive overview origins, generation, interplay among various components within TME. Furthermore, discuss pivotal role reshaping TME during tumorigenesis their specific cargo, such PD-1 non-coding RNA, which influence phenotypes critical cells Additionally, summarize applications different anti-tumor therapies, latest advancements engineering cancer immunotherapy, challenges encountered translation. light these findings, advocate broader understanding impact on TME, will unveil overlooked vulnerabilities potentially enhance existing immunotherapies.

Язык: Английский

Процитировано

47
The balance of STING signaling orchestrates immunity in cancer DOI

Klara Rasmussen Bollerup Lanng,

Emil Leth Lauridsen,

Martin R. Jakobsen

и другие.

Nature Immunology, Год журнала: 2024, Номер 25(7), С. 1144 - 1157

Опубликована: Июнь 25, 2024

Язык: Английский

Процитировано

46
Profiling cell identity and tissue architecture with single-cell and spatial transcriptomics DOI
Gunsagar S. Gulati,

Jeremy Philip D’Silva,

Yunhe Liu

и другие.

Nature Reviews Molecular Cell Biology, Год журнала: 2024, Номер 26(1), С. 11 - 31

Опубликована: Авг. 21, 2024

Язык: Английский

Процитировано

45
Open-ST: High-resolution spatial transcriptomics in 3D DOI

Marie Schott,

Daniel León-Periñán, Elena Splendiani

и другие.

Cell, Год журнала: 2024, Номер 187(15), С. 3953 - 3972.e26

Опубликована: Июнь 24, 2024

Язык: Английский

Процитировано

42
Spatially Segregated Macrophage Populations Predict Distinct Outcomes in Colon Cancer DOI Creative Commons
Magdalena Matusiak, John W. Hickey, David G.P. van IJzendoorn

и другие.

Cancer Discovery, Год журнала: 2024, Номер 14(8), С. 1418 - 1439

Опубликована: Март 27, 2024

Abstract Tumor-associated macrophages are transcriptionally heterogeneous, but the spatial distribution and cell interactions that shape macrophage tissue roles remain poorly characterized. Here, we spatially resolve five distinct human populations in normal malignant breast colon reveal their cellular associations. This map reveals reside segregated micro-environmental niches with conserved compositions repeated across healthy diseased tissue. We show IL4I1+ phagocytose dying cells areas high turnover predict good outcome cancer. In contrast, SPP1+ enriched hypoxic necrotic tumor regions portend worse A subset of FOLR2+ is embedded plasma niches. NLRP3+ co-localize neutrophils activate an inflammasome tumors. Our findings indicate a limited number unique function as fundamental building blocks Significance: work broadens our understanding different may exert on cancer growth potential predictive markers population-specific therapy targets.

Язык: Английский

Процитировано

34
PD-L1-expressing tumor-associated macrophages are immunostimulatory and associate with good clinical outcome in human breast cancer DOI Creative Commons
Lei Wang, Weihua Guo, Guo Zhikun

и другие.

Cell Reports Medicine, Год журнала: 2024, Номер 5(2), С. 101420 - 101420

Опубликована: Фев. 1, 2024

Tumor-associated macrophages (TAMs) are the predominant cells that express programmed cell death ligand 1 (PD-L1) within human tumors in addition to cancer cells, and PD-L1

Язык: Английский

Процитировано

30
Metabolic targeting of cancer associated fibroblasts overcomes T-cell exclusion and chemoresistance in soft-tissue sarcomas DOI Creative Commons

Marina T. Broz,

Emily Ko,

Kristin Ishaya

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Март 20, 2024

T cell-based immunotherapies have exhibited promising outcomes in tumor control; however, their efficacy is limited immune-excluded tumors. Cancer-associated fibroblasts (CAFs) play a pivotal role shaping the microenvironment and modulating immune infiltration. Despite identification of distinct CAF subtypes using single-cell RNA-sequencing (scRNA-seq), functional impact on hindering T-cell infiltration remains unclear, particularly soft-tissue sarcomas (STS) characterized by low response rates to therapies. In this study, we characterize STS murine models (in female mice) with composition scRNA-seq, identify subset CAFs termed glycolytic cancer-associated (glyCAF). GlyCAF rely GLUT1-dependent expression CXCL16 impede cytotoxic into parenchyma. Targeting glycolysis decreases restrictive glyCAF accumulation at margin, thereby enhancing augmenting chemotherapy. These findings highlight avenues for combinatorial therapeutic interventions possibly other solid Further investigations clinical trials are needed validate these potential strategies translate them practice.

Язык: Английский

Процитировано

30