CD25high Effector Regulatory T Cells Hamper Responses to PD-1 Blockade in Triple-Negative Breast Cancer DOI Creative Commons
Stéphane Fattori, Aude Le Roy, Jemila Houacine

et al.

Cancer Research, Journal Year: 2023, Volume and Issue: 83(18), P. 3026 - 3044

Published: June 28, 2023

Abstract Regulatory T cells (Treg) impede effective antitumor immunity. However, the role of Tregs in clinical outcomes patients with triple-negative breast cancer (TNBC) remains controversial. Here, we found that an immunosuppressive TNBC microenvironment is marked by imbalance between effector αβCD8+ and harboring hallmarks highly suppressive (eTreg). Intratumoral eTregs strongly expressed PD-1 persisted resistant to blockade. Importantly, CD25 was most selective surface marker primary metastases compared other candidate targets for eTreg depletion currently being evaluated trials advanced TNBC. In a syngeneic model, use Fc-optimized, IL2 sparing, anti-CD25 antibodies synergized blockade promote systemic immunity durable tumor growth control increasing T-cell/Treg ratios tumors periphery. Together, this study provides rationale translation therapy improve responses Significance: An CD8+ CD25high marks microenvironments αPD-1–resistant can be reversed through Treg increase αPD-1 efficacy.

Language: Английский

Metastatic colorectal cancer: mechanisms and emerging therapeutics DOI Creative Commons
Alice E. Shin, Filippo G. Giancotti,

Anil K. Rustgi

et al.

Trends in Pharmacological Sciences, Journal Year: 2023, Volume and Issue: 44(4), P. 222 - 236

Published: Feb. 23, 2023

Language: Английский

Citations

272
The Colorectal Cancer Tumor Microenvironment and Its Impact on Liver and Lung Metastasis DOI Open Access
Raghav Chandra, John D. Karalis, C. Liu

et al.

Cancers, Journal Year: 2021, Volume and Issue: 13(24), P. 6206 - 6206

Published: Dec. 9, 2021

Colorectal cancer (CRC) is the third most common malignancy and second cause of cancer-related mortality worldwide. A total 20% CRC patients present with distant metastases, frequently to liver lung. In primary tumor, as well at each metastatic site, cellular components tumor microenvironment (TME) contribute engraftment metastasis. These include immune cells (macrophages, neutrophils, T lymphocytes, dendritic cells) stromal (cancer-associated fibroblasts endothelial cells). this review, we highlight how TME influences progression invasion site its function in fostering niches lungs. We also discuss emerging clinical strategies target TME.

Language: Английский

Citations

108
Chronic inflammation, cancer development and immunotherapy DOI Creative Commons

Yalei Wen,

Ying‐Jie Zhu, Caishi Zhang

et al.

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 14, 2022

Chronic inflammation plays a pivotal role in cancer development. Cancer cells interact with adjacent cellular components (pro-inflammatory cells, intrinsic immune stromal etc.) and non-cellular to form the inflammatory tumor microenvironment (TME). Interleukin 6 (IL-6), macrophage migration inhibitory factor (MIF), checkpoint factors other pro-inflammatory cytokines produced by TME are main mediators of intercellular communication TME, which link chronic stimulating different oncogenic signaling pathways improving escape promote In parallel, ability monocytes, T regulatory (Tregs) B (Bregs) perform homeostatic tolerogenic functions is hijacked leading local or systemic immunosuppression. Standard treatments for advanced malignancies such as chemotherapy radiotherapy have improved last decades. However, clinical outcomes certain malignant cancers not satisfactory due drug resistance side effects. The application therapy (ICT) has brought hope treatment, although therapeutic efficacy still limited immunosuppressive microenvironment. Emerging evidences reveal that ideal therapies including clearance disruption tumor-induced immunosuppression targeting suppressive well reactivation anti-tumor ICT. Here, we review impacts major their downstream molecules on We also discuss important management cancer.

Language: Английский

Citations

103
Modulating Treg stability to improve cancer immunotherapy DOI Open Access

Jee Hye Kang,

Roberta Zappasodi

Trends in cancer, Journal Year: 2023, Volume and Issue: 9(11), P. 911 - 927

Published: Aug. 17, 2023

Language: Английский

Citations

70
Expanded ROS Generation and Hypoxia Reversal: Excipient‐free Self‐assembled Nanotheranostics for Enhanced Cancer Photodynamic Immunotherapy DOI

Jing Yang,

Bibo Ren,

Xuntao Yin

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(30)

Published: May 12, 2024

The efficacy of photodynamic therapy (PDT)-related cancer therapies is significantly restricted by two irreconcilable obstacles, i.e., low reactive oxygen species (ROS) generation capability and hypoxia which constrains the immune response. Herein, this work develops a self-assembled clinical photosensitizer indocyanine green (ICG) HSP90 inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) nanoparticles (ISDN) without any excipient. This discovers that hydrophobic interaction forces between ICG 17-DMAG promote photostability its intersystem crossing (ISC) process, thereby improving ROS quantum yield from 0.112 to 0.46. Augmented enhances PDT further immunogenic cell death (ICD) effects. inhibits HSP90/hypoxia-inducible factor 1α (HIF-1α) axis dramatically reverse immunosuppressive tumor microenvironment caused PDT-aggravated hypoxia. In mouse model pancreatic cancer, ISDN markedly improve cytotoxic T lymphocyte infiltration MHC I II activation, demonstrating superior ICD effects in situ powerful systematic antitumor immunity generation, eventually achieving vigorous recurrence resistance. study proposes an unsophisticated versatile strategy for enhancing systemic potentially extending it multiple cancers.

Language: Английский

Citations

34
Regulation of Treg cells by cytokine signaling and co-stimulatory molecules DOI Creative Commons
Yuan Zong,

Kaihang Deng,

Wai Po Chong

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: May 13, 2024

CD4 + CD25 Foxp3 regulatory T cells (Tregs), a vital component of the immune system, are responsible for maintaining homeostasis and preventing excessive responses. This review explores signaling pathways cytokines that regulate Treg cells, including transforming growth factor beta (TGF-β), interleukin (IL)-2, IL-10, IL-35, which foster differentiation enhance immunosuppressive capabilities Tregs. It also examines how, conversely, signals mediated by IL-6 tumor necrosis -alpha (TNF-α) can undermine suppressive functions or even drive their reprogramming into effector cells. The B7 family comprises indispensable co-stimulators cell activation. Among its members, this focuses on capacity CTLA-4 PD-1 to differentiation, function, survival As Tregs play an essential role in homeostasis, dysfunction contributes pathogenesis autoimmune diseases. delves potential employing Treg-based immunotherapy treatment diseases, transplant rejection, cancer. By shedding light these topics, article aims our understanding regulation therapeutic various pathological conditions.

Language: Английский

Citations

32
Exosome-mediated repair of spinal cord injury: a promising therapeutic strategy DOI Creative Commons
Tong Yu, Lili Yang, Ying Zhou

et al.

Stem Cell Research & Therapy, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 2, 2024

Abstract Spinal cord injury (SCI) is a catastrophic to the central nervous system (CNS) that can lead sensory and motor dysfunction, which seriously affects patients' quality of life imposes major economic burden on society. The pathological process SCI divided into primary secondary injury, cascade amplified responses triggered by injury. Due complexity mechanisms SCI, there no clear effective treatment strategy in clinical practice. Exosomes, are extracellular vesicles endoplasmic origin with diameter 30–150 nm, play critical role intercellular communication have become an ideal vehicle for drug delivery. A growing body evidence suggests exosomes great potential repairing SCI. In this review, we introduce exosome preparation, functions, administration routes. addition, summarize effect mechanism various repair review efficacy combination other strategies Finally, challenges prospects use described.

Language: Английский

Citations

17
Unleashing the Power of immune Checkpoints: A new strategy for enhancing Treg cells depletion to boost antitumor immunity DOI Creative Commons
Guoxin Li,

Siqi Li,

Yi Jiang

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 147, P. 113952 - 113952

Published: Jan. 6, 2025

Regulatory T (Treg) cells, immunosuppressive CD4+ can impede anti-tumor immunity, complicating cancer treatment. Since their discovery, numerous studies have been dedicated to understand Treg cell biology, with a focus on checkpoint pathways' role in generation and function. Immune checkpoints, such as PD-1/PD-L1, CTLA-4, TIGIT, TIM-3, OX40, are pivotal controlling expansion activity the tumor microenvironment (TME), affecting ability suppress immune responses. This review examines complex relationship between these checkpoints Tregs TME, how they influence immunity. We also discuss therapeutic potential of targeting enhance including use blockade (ICB) therapies novel approaches CCR8-targeted therapies. Understanding interaction cells lead more effective immunotherapeutic strategies, combining inhibitors, improve patient outcomes

Language: Английский

Citations

2
Chemotherapeutics-enabled apoptosis-pyroptosis switch to trigger adaptive and innate immunity for metastatic breast cancer immunotherapy DOI
Yingtao Zhong,

Ziwen Qiu,

Keyan Zhang

et al.

Materials Today, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

2
Brd7 loss reawakens dormant metastasis initiating cells in lung by forging an immunosuppressive niche DOI Creative Commons
Jayanta Mondal, Junfeng Zhang,

Qing Feng

et al.

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

Published: Feb. 5, 2025

Metastasis in cancer is influenced by epigenetic factors. Using an vivo screen, we demonstrate that several subunits of the polybromo-associated BAF (PBAF) chromatin remodeling complex, particularly Brd7, are required for maintaining breast metastatic dormancy lungs female mice. Brd7 loss induces reawakening, along with modifications epigenomic landscapes and upregulated oncogenic signaling. Breast cells harboring inactivation also reprogram surrounding immune microenvironment downregulating MHC-1 expression promoting a pro-metastatic cytokine profile. Flow cytometric single-cell analyses reveal increased levels pro-tumorigenic inflammatory transitional neutrophils, CD8+ exhausted T cells, CD4+ stress response from mice Brd7-deficient metastases. Finally, attenuating this immunosuppressive milieu neutrophil depletion, extracellular trap (NET) inhibition, or checkpoint therapy abrogates outgrowth. These findings implicate PBAF triggering outgrowth cancer, pointing to targetable underlying mechanisms involving specific cell compartments. Metastasis-initiating can reawaken dormant state initially allowed them survive, Here, authors show promotes tumor drives reawakening lung.

Language: Английский

Citations

2