High tumor glucocorticoid receptor expression in early-stage, triple-negative breast cancer is associated with increased T-regulatory cell infiltration DOI Creative Commons
Margarite D. Matossian,

Christine Y. Shiang,

D. Nesli Dolcen

et al.

Breast Cancer Research and Treatment, Journal Year: 2024, Volume and Issue: 209(3), P. 563 - 572

Published: Nov. 23, 2024

In early-stage, triple-negative breast cancer (TNBC), immune cell infiltration contributes to survival, tumor invasion, and metastasis. High TNBC glucocorticoid receptor (GR) expression in early-stage is associated with poor long-term outcomes; it unknown if high GR an immunosuppressed microenvironment. We hypothesized that would be immune-suppressed microenvironment, which could thus account for the prognosis observed GR-positive TNBC. Formalin fixed-paraffin embedded tissue (n = 47) from patients diagnosed The University of Chicago (2002-2014) were evaluated both anti-GR immunohistochemistry infiltrating cells by immunofluorescence. Multiplexed antibodies used enumerate CD8+, FOXP3+, BATF3+ within pan-cytokeratin positive regions interest, nonparametric tests compared absolute counts each these tumor-infiltrating types. average age represented this study was 52 years, 63% self-identified as Black. There no significant association between age, race, or clinical stage at diagnosis. Compared GR-low tumors, treatment-naïve relatively increased numbers immunosuppressive FOXP3 + regulatory T (p 0.046) BATF3+immune 0.021). While there a correlation CD8+ infiltration, not 0.068). ratio CD8+/FOXP3+cells also 0.24). These data support hypothesis TNBC, significantly cells, suggesting tumor-intrinsic role shaping milieu. Furthermore, suppression activity may regulate microenvironment improve outcomes GR-high

Language: Английский

Biological and clinical significance of tumour-infiltrating lymphocytes in the era of immunotherapy: a multidimensional approach DOI
Miguel López de Rodas, María Villalba, Miguel F. Sanmamed

et al.

Nature Reviews Clinical Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 16, 2025

Language: Английский

Citations

5
Antigen-presenting cancer associated fibroblasts enhance antitumor immunity and predict immunotherapy response DOI Creative Commons
Junquan Song,

Rongyuan Wei,

Chenchen Liu

et al.

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

Published: March 4, 2025

Cancer-associated fibroblasts (CAF) play a crucial role in tumor progression and immune regulation. However, the functional heterogeneity of CAFs remains unclear. Here, we identify antigen-presenting (apCAF), characterized by high MHC II expression, gastric cancer (GC) tumors find that apCAFs are preferentially located near tertiary lymphoid structures. Both vivo vitro experiments demonstrate promote T cell activation enhances its cytotoxic proliferative capacities, thereby strengthening cell-mediated anti-tumor immunity. Additionally, facilitate polarization macrophages toward pro-inflammatory phenotype. These polarized macrophages, turn, formation apCAFs, creating positive feedback loop amplifies responses. Notably, baseline immunotherapy responders across various types exhibit higher levels infiltration. This study advances understanding GC highlights as potential biomarker for predicting response pan-cancer.

Language: Английский

Citations

2
Unraveling UPR-Mediated Intercellular Crosstalk: Implications for Immunotherapy Resistance Mechanisms DOI
Lu Si, Qimin Zhou, Rongjie Zhao

et al.

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217613 - 217613

Published: March 1, 2025

Language: Английский

Citations

2
The complexity of immune evasion mechanisms throughout the metastatic cascade DOI

Nicole M. Haynes,

Thomas B Chadwick, Belinda S. Parker

et al.

Nature Immunology, Journal Year: 2024, Volume and Issue: 25(10), P. 1793 - 1808

Published: Sept. 16, 2024

Language: Английский

Citations

10
Immunometabolism: signaling pathways, homeostasis, and therapeutic targets DOI Creative Commons
Rongrong Xu, Xiaobo He, Jia Xu

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(11)

Published: Nov. 1, 2024

Abstract Immunometabolism plays a central role in sustaining immune system functionality and preserving physiological homeostasis within the organism. During differentiation activation, cells undergo metabolic reprogramming mediated by complex signaling pathways. Immune maintain are influenced microenvironmental cues. A series of immunometabolic enzymes modulate cell function metabolizing nutrients accumulating products. These reverse cells’ differentiation, disrupt intracellular pathways, regulate responses, thereby influencing disease progression. The huge population enzymes, ubiquity, complexity regulation have kept mechanisms related to many diseases from being discovered, what has been revealed so far is only tip iceberg. This review comprehensively summarized enzymes’ multiple such as T cells, macrophages, natural killer dendritic cells. By classifying dissecting immunometabolism implications diseases, summarizing analyzing advancements research clinical applications inhibitors targeting these this intended provide new perspective concerning for understanding system, offer novel insight into future therapeutic interventions.

Language: Английский

Citations

4
Eosinophils Enhance Granuloma-Mediated Control of Persistent Salmonella Infection DOI Creative Commons
Denise M. Monack, Daniel Butler, Blanda Di Luccia

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

Abstract Salmonella enterica can persist asymptomatically within tissues for extended periods. This remarkable feat is achieved through intricate host-pathogen interactions in immune cell aggregates called granulomas, wherein Salmonella find favorable cellular niches to exploit while the host limits its expansion and tissue dissemination. Here, using a mouse model of persistent infection, we identify host-protective role eosinophils control Typhimurium (STm) infection mesenteric lymph nodes (MLN), main lymphoid STm persistence. Combining spatial transcriptomics experimental manipulations, found that macrophages responding recruited C-C motif chemokine ligand 11 (CCL11)-dependent manner enhanced their activation. Eosinophil deficiencies increased burdens, which was associated with altered granuloma size impaired type-1 immunity MLN. Thus, play vital restraining exploitation at key site bacterial

Language: Английский

Citations

0
ImmunOctoberfest reloaded DOI
Anna M. Schulz, Caitlin C. Zebley, Ben Youngblood

et al.

Nature Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 24, 2025

Language: Английский

Citations

0
An Iron‐Polyphenol Decorated siRNA‐Encapsulated Nanomedicine Multifacetedly Promoted Macrophage Phagocytosis for Synergistic Ferroptosis‐Immunotherapy DOI Open Access

Boya Yu,

Zekai Xiao,

Shuaiqi Shao

et al.

Advanced Functional Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 26, 2025

Abstract Macrophages are vital components of the innate immune system, capable directly engulfing tumor cells. However, cells can cunningly evade recognition and phagocytosis by macrophages. In light this, an iron‐polyphenol‐decorated poly(ethylene glycol)‐poly(lactic‐co‐glycolic acid (PEG‐PLGA) nanoparticle has been developed with efficient siRNA encapsulation (NP siCD47 @Fe‐TA) to trigger ferroptosis in cell also elicit macrophage‐mediated immunotherapy. The Fe‐TA (Tannic acid) shell NP @Fe‐TA induces cell, which consequently produces oxygenated phosphatidylethanolamine 1‐steaoryl‐2‐15‐HpETE‐sn‐glycero‐3‐phosphatidylethanolamine (SAPE‐OOH) membrane achieve surface exposure calreticulin (CRT). Meanwhile, encapsulated efficiently down‐regulates CD47 receptor membrane. SAPE‐OOH CRT down‐regulation remarkably promoted macrophage elicited systemic anticancer response. Eventually, suppress growth. Moreover, after combination checkpoint blockade (ICB) antibody, inhibits progress metastasis cold triple‐negative 4T1 breast cancer model.

Language: Английский

Citations

0
Biosynthetic plasticity enables CD8+ T cell functional resilience under nutrient stress DOI Creative Commons
Michael Scaglione, Montana Knight, Krittin Trihemasava

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 24, 2025

Summary / Abstract To maintain lineage-specific functions, cells must acquire and allocate nutrients across diverse cellular processes, even in metabolically-dysregulated environments. The mechanisms allowing CD8+ T to immune function perturbed environments are poorly understood. We find that adapt nutrient stresses over time, reconfiguring gene-regulatory metabolic networks license functional recovery. Under acute stress, reorient translational programming, limiting demand while prioritizing stress-sensitive transcriptional responses. Within these responses, the transcription factors ATF4 CEBPG jointly establish an adaptive program, promoting amino acid synthesis uptake maintaining mitochondrial anaplerosis. Despite diminished energetic capacity under environmental this program prevents failure of central carbon metabolism, mitigating stress amplification dysfunction potentiate anti-tumor immunity. Altogether, we demonstrate biosynthetic plasticity via reprioritization confers resilience unfavorable environments, offering novel strategies enhance immunotherapies.

Language: Английский

Citations

0
Highly Efficient Bifunctional Peptides for Tumor Immunotherapy by Simultaneously Activating T Cells and Blocking PD-L1 Immune Checkpoint DOI
Aixian Zheng, Xiaorong Wang, Yuling Wu

et al.

ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: unknown

Published: March 15, 2025

Immune checkpoint inhibitors represented by PD-1/PD-L1 monoclonal antibodies have shown great success in tumor immunotherapy. However, the response rate of immune blockade (ICB) therapy alone is far from satisfactory due to insufficient and exhausted tumor-infiltrating T cells. Meanwhile, antibody-based drugs some drawbacks such as high cost complicated preparation, which require further development nonantibody more rational strategies for improving effectiveness treatment. Here, a highly efficient bifunctional peptide (Bi-pep) was constructed treatment simultaneously activating cells blocking PD-L1 checkpoint. This not only can block immunosuppressive pathway but also directly efficiently promote activation proliferation cells, thereby showing significant effect on promoting cell killing The Bi-pep-induced antitumor verified both subcutaneous orthotopic models, significantly inhibit growth thus prolong survival tumor-bearing mice, holding potential biomedical applications.

Language: Английский

Citations

0