Nature reviews. Immunology, Journal Year: 2023, Volume and Issue: 23(8), P. 522 - 538
Published: Feb. 7, 2023
Language: Английский
The Journal of Experimental Medicine, Journal Year: 2021, Volume and Issue: 219(2)
Published: Dec. 17, 2021
Tumor-associated macrophages (TAMs) are correlated with the progression of prostatic adenocarcinoma (PCa). The mechanistic basis this correlation and therapeutic strategies to target TAMs in PCa remain poorly defined. Here, single-cell RNA sequencing was used profile transcriptional landscape human PCa, leading identification a subset characterized by dysregulation pathways associated lipid metabolism. This correlates positively shorter disease-free survival is an accumulation lipids that dependent on Marco. Mechanistically, cancer cell–derived IL-1β enhances Marco expression macrophages, reciprocally, cell migration promoted CCL6 released lipid-loaded TAMs. Moreover, administration high-fat diet tumor-bearing mice raises abundance Finally, targeting blockade hinders tumor growth invasiveness improves efficacy chemotherapy models pointing combinatorial may influence patient outcomes.
Language: Английский
Citations
113
Trends in cancer, Journal Year: 2022, Volume and Issue: 8(7), P. 517 - 526
Published: March 12, 2022
Language: Английский
Citations
105
Gut, Journal Year: 2022, Volume and Issue: 72(2), P. 325 - 337
Published: June 15, 2022
Objective Programmed cell death protein 1 (PD-1) checkpoint inhibition and adoptive cellular therapy have had limited success in patients with microsatellite stable colorectal cancer liver metastases (CRLM). We sought to evaluate the effect of interleukin 10 (IL-10) blockade on endogenous T chimeric antigen receptor (CAR-T) antitumour function CRLM slice cultures. Design created organotypic cultures from human (n=38 patients’ tumours) tested effects a neutralising antibody against IL-10 (αIL-10) both alone as treatment combination exogenously administered carcinoembryonic (CEA)-specific CAR-T cells. evaluated single multiplex immunohistochemistry, situ hybridisation, single-cell RNA sequencing, reverse-phase arrays time-lapse fluorescent microscopy. Results αIL-10 generated 1.8-fold increase cell-mediated carcinoma significantly increased proportions CD8 + cells without exhaustion transcription changes, leukocyte - DR isotype (HLA-DR) expression macrophages. The were reversed by major histocompatibility complex class I or II (MHC-I MHC-II) blockade, confirming essential role presenting Interrupting signalling also rescued murine proliferation cytotoxicity myeloid immunosuppression. In slices, CEA-specific activation cytotoxicity, nearly 70% apoptosis across multiple tumours. Pretreatment an blocking potentiated function. Conclusion Neutralising has therapeutic potential stand-alone augment adoptively transferred
Language: Английский
Citations
91
Clinical Cancer Research, Journal Year: 2022, Volume and Issue: 29(1), P. 244 - 260
Published: Oct. 14, 2022
Abstract Purpose: The liver is the most frequent metastatic site for colorectal cancer. Its microenvironment modified to provide a niche that conducive cancer cell growth. This study focused on characterizing cellular changes in (mCRC) tumor (TME). Experimental Design: We analyzed series of microsatellite stable (MSS) mCRCs liver, paired normal tissue, and peripheral blood mononuclear cells using single-cell RNA sequencing (scRNA-seq). validated our findings multiplexed spatial imaging bulk gene expression with deconvolution. Results: identified TME-specific SPP1-expressing macrophages altered metabolism features, foam characteristics, increased activity extracellular matrix (ECM) organization. SPP1+ fibroblasts expressed complementary ligand–receptor pairs potential mutually influence their gene-expression programs. TME lacked dysfunctional CD8 T contained regulatory cells, indicative immunosuppression. Spatial these states TME. Moreover, had close proximity, which requirement intercellular communication networking. In an independent cohort we confirmed presence data. An proportion was associated worst prognosis patients. Conclusions: demonstrated mCRC characterized by transcriptional alterations Intercellular networking between supports growth immunosuppressed liver. These features can be used target immune-checkpoint–resistant MSS tumors.
Language: Английский
Citations
91
Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)
Published: Jan. 25, 2024
Abstract Drug-eluting stent implantation suppresses the excessive proliferation of smooth muscle cells to reduce in-stent restenosis. However, efficacy drug-eluting stents remains limited due delayed reendothelialization, impaired intimal remodeling, and potentially increased late Here, we show that a drug-free coating formulation functionalized with tailored recombinant humanized type III collagen exerts one-produces-multi effects in response injured tissue following implantation. We demonstrate possesses anticoagulation, anti-inflammatory, hyperplasia suppression properties. perform transcriptome analysis indicate favors endothelialization process induces conversion contractile phenotype. find compared stents, our reduces restenosis rabbit porcine models improves vascular neointimal healing model. Collectively, system represents promising strategy for next-generation stents.
Language: Английский
Citations
28
Cancer Cell, Journal Year: 2024, Volume and Issue: 42(5), P. 747 - 758
Published: April 25, 2024
Language: Английский
Citations
23
Nature reviews. Immunology, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 2, 2025
Language: Английский
Citations
8
Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)
Published: Jan. 8, 2025
Tumor-associated macrophages (TAMs) are pivotal immune cells within the tumor microenvironment (TME), exhibiting dual roles across various cancer types. Depending on context, TAMs can either suppress progression and weaken drug sensitivity or facilitate growth drive therapeutic resistance. This study explores whether targeting of head neck squamous cell carcinoma (HNSCC) improve efficacy chemotherapy. Bioinformatics analyses were performed to evaluate infiltration levels in HNSCC tissues examine their associations with patients' clinicopathological characteristics prognosis. Flow cytometry was utilized measure expression key macrophage markers assess apoptosis following treatment colony stimulating factor 1 receptor (CSF1R) inhibitors (BLZ945, PLX3397). Additionally, immunohistochemistry employed detect CD68 CD8 expression. In vivo, antitumor CSF1R tested mouse model, both as monotherapy combination cisplatin, potential synergistic effects. Bioinformatic analysis identified predominant infiltrating TME HNSCC, significantly higher compared adjacent non-tumor tissues. High associated poorer overall survival (OS), disease-free (DFS), human papillomavirus (HPV) infection status, advanced disease stages. The TAMs-related genes prediction model demonstrated high prognostic accuracy. is primarily expressed TAMs, where may antigen binding activation. vitro experiments showed that induce apoptosis, enhance phagocytic activity, reduce CD206 IL-10 secretion, thereby diminishing immunosuppressive function. vivo revealed while alone had limited suppressing growth, cisplatin enhanced efficacy, evidenced by increased CD8+ T TME. Targeting via inhibition enhances HNSCC. These findings suggest hold promise a component therapy for
Language: Английский
Citations
3
Cancer Research, Journal Year: 2021, Volume and Issue: 81(20), P. 5284 - 5295
Published: Aug. 13, 2021
Abstract While macrophages are among the most abundant immune cell type found within primary and metastatic mammary tumors, how their complexity heterogeneity change with progression remains unknown. Here, were isolated from lungs of mice bearing orthotopic tumors for single-cell RNA sequencing (scRNA-seq). Seven distinct macrophage clusters identified, including populations exhibiting enhanced differential expression genes related to antigen presentation (H2-Aa, Cd74), cycle (Stmn1, Cdk1), interferon signaling (Isg15, Ifitm3). Interestingly, one cluster demonstrated a profile concordant lipid-associated (Lgals3, Trem2). Compared nontumor-bearing controls, number these cells per gram tissue was significantly increased in tumor-bearing mice, vast majority costaining positively alveolar marker Siglec-F. Enrichment implicated pathways lipid metabolism as well extracellular matrix remodeling immunosuppression observed. In addition, displayed reduced capacity phagocytosis. Collectively, findings highlight diversity present lesions characterize subset previously unidentified lung metastases. Significance: scRNA-seq metastases reveals extensive identifies novel subpopulation enriched involved metabolism, remodeling, immunosuppression.
Language: Английский
Citations
72
Journal of Experimental & Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 42(1)
Published: July 22, 2023
Colorectal cancer liver metastasis (CRLM) is one of the leading causes death among patients with colorectal (CRC). Although immunotherapy has demonstrated encouraging outcomes in CRC, its benefits are minimal CRLM. The complex immune landscape hepatic tumour microenvironment essential for development a premetastatic niche and colonisation CRC cells; thus, an in-depth understanding these mechanisms can provide effective immunotherapeutic targets This review summarises recent studies on CRLM highlights therapeutic prospects targeting suppressive
Language: Английский
Citations
41