Tebentafusp, a T cell engager, promotes macrophage reprogramming and in combination with IL-2 overcomes macrophage immunosuppression in cancer DOI Creative Commons
Esra Güç, Agatha Treveil, Emma Leach

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 10, 2025

Uveal melanoma (UM) is the most common intraocular cancer in adults, with metastatic disease (mUM) occurring approximately half of patients. Tebentafusp, an immune-mobilizing monoclonal T cell receptor against (ImmTAC), a therapeutic shown to improve overall survival (OS) HLA-A*02:01+ adult patients mUM. Here we investigate impact tumor-associated macrophages (TAM) on ImmTAC activity. In vitro, M2 inhibit ImmTAC-mediated tumor-killing dose-dependent and contact-dependent manner. Accordingly, high baseline intratumoral TAM-to-T ratios correlate shorter OS (HR = 2.09, 95% CI, 1.31–3.33, p 0.002) tebentafusp-treated mUM from phase 2 trial. By contrast, IL-2 conditioning cells overcomes macrophage-mediated suppression while treatment leads M2-to-M1 macrophage reprogramming both vitro Overall, show that tebentafusp reshapes tumor microenvironment enhance anti-tumor activity, whilst combining may benefit levels TAM. 'T engagers promote antitumor immunity, but how modulates this activity still unclear. authors show, using biopsies uveal single analyses, engager, tebentafusp, reprograms ameliorates, synergy IL-2, immunosuppression cancer.

Language: Английский

The cancer-immunity cycle: Indication, genotype, and immunotype DOI Creative Commons
Ira Mellman, Daniel S. Chen, Thomas Powles

et al.

Immunity, Journal Year: 2023, Volume and Issue: 56(10), P. 2188 - 2205

Published: Oct. 1, 2023

The cancer-immunity cycle provides a framework to understand the series of events that generate anti-cancer immune responses. It emphasizes iterative nature response where killing tumor cells by T initiates subsequent rounds antigen presentation and cell stimulation, maintaining active immunity adapting it evolution. Any step can become rate-limiting, rendering system unable control growth. Here, we update based on remarkable progress past decade. Understanding mechanism checkpoint inhibition has evolved, as our view dendritic in sustaining anti-tumor immunity. We additionally account for role microenvironment facilitating, not just suppressing, response, discuss importance considering tumor's immunological phenotype, "immunotype". While these new insights add some complexity cycle, they also provide targets research therapeutic intervention.

Language: Английский

Citations

363
CD8+ T cells in the cancer-immunity cycle DOI Creative Commons
Josephine R. Giles, Anna-Maria Globig,

Susan M. Kaech

et al.

Immunity, Journal Year: 2023, Volume and Issue: 56(10), P. 2231 - 2253

Published: Oct. 1, 2023

Language: Английский

Citations

168
Roles of macrophages in tumor development: a spatiotemporal perspective DOI Creative Commons

Mathilde Bied,

William W. Ho, Florent Ginhoux

et al.

Cellular and Molecular Immunology, Journal Year: 2023, Volume and Issue: 20(9), P. 983 - 992

Published: July 10, 2023

Abstract Macrophages are critical regulators of tissue homeostasis but also abundant in the tumor microenvironment (TME). In both primary tumors and metastases, such tumor-associated macrophages (TAMs) seem to support development. While we know that TAMs dominant immune cells TME, their vast heterogeneity associated functions only just being unraveled. this review, outline various known TAM populations found thus far delineate specialized roles with main stages cancer progression. We discuss how may prime premetastatic niche enable growth a metastasis then subsequent metastasis-associated can secondary growth. Finally, speculate on challenges remain be overcome research.

Language: Английский

Citations

136
Current advance of nanotechnology in diagnosis and treatment for malignant tumors DOI Creative Commons

Bilan Wang,

Shiqi Hu, Yan Teng

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Aug. 12, 2024

Cancer remains a significant risk to human health. Nanomedicine is new multidisciplinary field that garnering lot of interest and investigation. shows great potential for cancer diagnosis treatment. Specifically engineered nanoparticles can be employed as contrast agents in diagnostics enable high sensitivity high-resolution tumor detection by imaging examinations. Novel approaches labeling are also made possible the use nanoprobes nanobiosensors. The achievement targeted medication delivery therapy accomplished through rational design manufacture nanodrug carriers. Nanoparticles have capability effectively transport medications or gene fragments tissues via passive active targeting processes, thus enhancing treatment outcomes while minimizing harm healthy tissues. Simultaneously, context radiation sensitization photothermal enhance therapeutic efficacy malignant tumors. This review presents literature overview summary how nanotechnology used According oncological diseases originating from different systems body combining pathophysiological features cancers at sites, we most recent developments applications. Finally, briefly discuss prospects challenges cancer.

Language: Английский

Citations

93
The intratumor mycobiome promotes lung cancer progression via myeloid-derived suppressor cells DOI Creative Commons
Ning‐Ning Liu, Chengxiang Yi,

Luqi Wei

et al.

Cancer Cell, Journal Year: 2023, Volume and Issue: 41(11), P. 1927 - 1944.e9

Published: Sept. 21, 2023

Language: Английский

Citations

85
Identification of hypoxic macrophages in glioblastoma with therapeutic potential for vasculature normalization DOI Creative Commons
Wenying Wang, Tianran Li, Yue Cheng

et al.

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(5), P. 815 - 832.e12

Published: April 18, 2024

Monocyte-derived tumor-associated macrophages (Mo-TAMs) intensively infiltrate diffuse gliomas with remarkable heterogeneity. Using single-cell transcriptomics, we chart a spatially resolved transcriptional landscape of Mo-TAMs across 51 patients isocitrate dehydrogenase (IDH)-wild-type glioblastomas or IDH-mutant gliomas. We characterize Mo-TAM subset that is localized to the peri-necrotic niche and skewed by hypoxic cues acquire hypoxia response signature. Hypoxia-TAM destabilizes endothelial adherens junctions activating adrenomedullin paracrine signaling, thereby stimulating hyperpermeable neovasculature hampers drug delivery in glioblastoma xenografts. Accordingly, genetic ablation pharmacological blockade produced restores vascular integrity, improves intratumoral concentration anti-tumor agent dabrafenib, achieves combinatorial therapeutic benefits. Increased proportion expression predictive tumor vessel hyperpermeability worse prognosis glioblastoma. Our findings highlight diversity spatial niche-steered reprogramming indicate potential therapeutics targeting normalize vasculature.

Language: Английский

Citations

48
The role of tumor-associated macrophages in tumor immune evasion DOI Creative Commons

Ruizhe Huang,

Ting Kang, Siyu Chen

et al.

Journal of Cancer Research and Clinical Oncology, Journal Year: 2024, Volume and Issue: 150(5)

Published: May 7, 2024

Abstract Background Tumor growth is closely linked to the activities of various cells in tumor microenvironment (TME), particularly immune cells. During progression, circulating monocytes and macrophages are recruited, altering TME accelerating growth. These adjust their functions response signals from stromal Tumor-associated (TAMs), similar M2 macrophages, key regulators TME. Methods We review origins, characteristics, TAMs within This analysis includes mechanisms through which facilitate evasion promote metastasis. Additionally, we explore potential therapeutic strategies that target TAMs. Results instrumental mediating malignant behaviors. They release cytokines inhibit effector attract additional immunosuppressive primarily T cells, inducing exhaustion directly, influencing activity indirectly cellular interactions, or suppressing checkpoints. directly involved proliferation, angiogenesis, invasion, Summary Developing innovative tumor-targeted therapies immunotherapeutic currently a promising focus oncology. Given pivotal role evasion, several approaches have been devised them. include leveraging epigenetics, metabolic reprogramming, engineering repolarize TAMs, inhibiting recruitment activity, using as drug delivery vehicles. Although some these remain distant clinical application, believe future targeting will offer significant benefits cancer patients.

Language: Английский

Citations

47
The Interplay between Extracellular Matrix Remodeling and Cancer Therapeutics DOI Creative Commons
Jai Prakash, Yuval Shaked

Cancer Discovery, Journal Year: 2024, Volume and Issue: 14(8), P. 1375 - 1388

Published: Aug. 2, 2024

Abstract The extracellular matrix (ECM) is an abundant noncellular component of most solid tumors known to support tumor progression and metastasis. interplay between the ECM cancer therapeutics opens up new avenues in understanding biology. While protect from anticancer agents by serving as a biomechanical barrier, emerging studies show that various therapies induce remodeling, resulting therapy resistance progression. This review discusses critical issues this field including how influences treatment outcome, affect challenges associated with targeting ECM. Significance: intricate relationship reveals novel insights into biology its effective treatment. may anti-cancer agents, recent research highlights paradoxical role therapy-induced remodeling promoting explores key aspects therapeutics.

Language: Английский

Citations

43
Radiotherapy and immunology DOI Creative Commons
Liangliang Wang, Connor Lynch, Sean P. Pitroda

et al.

The Journal of Experimental Medicine, Journal Year: 2024, Volume and Issue: 221(7)

Published: May 21, 2024

The majority of cancer patients receive radiotherapy during the course treatment, delivered with curative intent for local tumor control or as part a multimodality regimen aimed at eliminating distant metastasis. A major focus research has been DNA damage; however, in past two decades, emphasis shifted to important role immune system plays radiotherapy-induced anti-tumor effects. Radiotherapy reprograms microenvironment, triggering and RNA sensing cascades that activate innate immunity ultimately enhance adaptive immunity. In opposition, also induces suppression immunity, including recruitment regulatory T cells, myeloid-derived suppressor suppressive macrophages. balance pro- is regulated by chemokines cytokines. Microbiota can influence outcomes under clinical investigation. Blockade PD-1/PD-L1 axis CTLA-4 extensively investigated combination radiotherapy; we include review trials involving inhibition these checkpoints radiotherapy.

Language: Английский

Citations

28
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

et al.

Cell Reports Medicine, Journal Year: 2024, Volume and Issue: 5(2), P. 101420 - 101420

Published: Feb. 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

Language: Английский

Citations

27