Lactylation‐Driven NUPR1 Promotes Immunosuppression of Tumor‐Infiltrating Macrophages in Hepatocellular Carcinoma DOI Creative Commons

Jia-Liang Cai,

Peiling Zhang,

Yufan Cai

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 30, 2025

While checkpoint immunotherapy effectively mobilizes T-cell responses against tumors, its success in hepatocellular carcinoma (HCC) is frequently undermined by immunosuppressive myeloid cells within the tumor microenvironment. This study investigates role of nuclear protein 1 (NUPR1), a gene prominently expressed tumor-associated macrophages (TAMs), mediating this suppression and influencing outcomes. Through comprehensive analysis single-cell RNA sequencing (scRNA-seq) datasets functional assays vitro vivo, NUPR1 identified as critical regulator TAMs. The upregulation associated with enhanced M2 macrophage polarization increased expression immune checkpoints PD-L1 SIRPA, resulting CD8+ T cell exhaustion diminished response to immunotherapy. Mechanistically, inhibits ERK JNK signaling pathways, thereby creating an milieu conducive progression. Additionally, tumor-derived lactate shown upregulate via histone lactylation, perpetuating feedback loop that intensifies suppression. Pharmacological targeting reverses polarization, curtails growth, augments efficacy PD-1 blockade preclinical models, positioning both potential biomarker for responsiveness therapeutic target boost HCC.

Language: Английский

Hypericin impedes M2 macrophage polarization and protects against Hepatocellular carcinoma DOI

X. Y. Wen,

Xianling Wang, Qing Yao

et al.

Molecular Immunology, Journal Year: 2025, Volume and Issue: 181, P. 160 - 168

Published: March 29, 2025

Language: Английский

Citations

0
Nano-strategies for Targeting Tumor-Associated Macrophages in Cancer immunotherapy DOI Creative Commons
Qian Li, Jingwei Xu, Rong Hua

et al.

Journal of Cancer, Journal Year: 2025, Volume and Issue: 16(7), P. 2261 - 2274

Published: March 31, 2025

Tumor-associated macrophages (TAMs) are one type of the most abundant immune cells within tumor, resulting in immunosuppresive tumor microenvironment and resistance to immunotherapy. Thus, targeting TAMs is a promising therapeutic strategy for boosting cancer This study provides an overview current strategies TAMs, which focus on blocking recruitment by tumors, regulating polarization directly eliminating using various nanodrugs, especially with new categorization based specific signaling pathways, such as NF-κB, HIF-1α, ROS, STAT, JNK, PI3K, Notch involved their regulatory mechanism. The latest developments nanodrugs modulating these pathways discussed determining role microenvironment. Despite challenges clinical translation complexity nanodrug synthesis, potential enhancing effectiveness immunotherapy worthy expecting.

Language: Английский

Citations

0
Multifunctional Nanoplatform Based on Gelatin Nanoparticles with Immunomodulatory Capabilities for Combined Immunotherapy and Chemotherapy of Melanoma DOI

Ying Chen,

Miaomiao Zhang,

Zongjia Li

et al.

Biomacromolecules, Journal Year: 2025, Volume and Issue: unknown

Published: April 10, 2025

Tumor immunotherapy has shown considerable therapeutic potential, especially when combined with chemotherapy. In this study, we developed a multifunctional nanoplatform GNPs-DOX/R848 that and chemotherapy for the treatment of melanoma, in which gelatin nanoparticles (GNPs) were loaded immunomodulatory agent resiquimod (R848) drug doxorubicin (DOX). GNPs possessed inherent properties; R848, they induced more pronounced polarization M1-like macrophages by activating NF-κB signaling pathway, thereby reversing immunosuppressive tumor microenvironment. Meanwhile, effectively delivered R848 DOX to cells, promoting stronger effects drugs, strongly immunogenic cell death triggered DOX, leading infiltration T cells into tissue. The melanoma demonstrated significantly reduced volume, enhanced chemotherapy, providing new approach cancer

Language: Английский

Citations

0
Peritoneal resident macrophages constitute an immunosuppressive environment in peritoneal metastasized colorectal cancer DOI Creative Commons
J Saris, Andrew Y. F. Li Yim,

S. Bootsma

et al.

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

Published: April 17, 2025

Patients with peritoneal metastasized colorectal cancer (PM-CRC) have a dismal prognosis. We hypothesized that an immunosuppressive environment in the cavity underlies poor define composition of human immune system (PerIS) using single-cell technologies 18 patients with- and without PM-CRC, as well matched metastases (n = 8). Here we show PerIS contains abundant C1Q+VSIG4+ SPP1+VSIG4+ peritoneal-resident macrophages (PRMs), monocyte-like (mono-CMs), which share features tumor-associated macrophages, even homeostasis. In expression cytokines IL10 VEGF increases, while simultaneously antigen-presenting molecules decreases PRMs. These intratumoral suppressive PRMs originate from PerIS, intraperitoneal depletion vivo anti-CSF1R combined anti-PD1 significantly reduces tumor burden improves survival. Thus, metastatic site-specific niche, targeting is promising treatment strategy for PM-CRC.

Language: Английский

Citations

0
Lactylation‐Driven NUPR1 Promotes Immunosuppression of Tumor‐Infiltrating Macrophages in Hepatocellular Carcinoma DOI Creative Commons

Jia-Liang Cai,

Peiling Zhang,

Yufan Cai

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 30, 2025

While checkpoint immunotherapy effectively mobilizes T-cell responses against tumors, its success in hepatocellular carcinoma (HCC) is frequently undermined by immunosuppressive myeloid cells within the tumor microenvironment. This study investigates role of nuclear protein 1 (NUPR1), a gene prominently expressed tumor-associated macrophages (TAMs), mediating this suppression and influencing outcomes. Through comprehensive analysis single-cell RNA sequencing (scRNA-seq) datasets functional assays vitro vivo, NUPR1 identified as critical regulator TAMs. The upregulation associated with enhanced M2 macrophage polarization increased expression immune checkpoints PD-L1 SIRPA, resulting CD8+ T cell exhaustion diminished response to immunotherapy. Mechanistically, inhibits ERK JNK signaling pathways, thereby creating an milieu conducive progression. Additionally, tumor-derived lactate shown upregulate via histone lactylation, perpetuating feedback loop that intensifies suppression. Pharmacological targeting reverses polarization, curtails growth, augments efficacy PD-1 blockade preclinical models, positioning both potential biomarker for responsiveness therapeutic target boost HCC.

Language: Английский

Citations

0