1-Pyrroline-5-carboxylate inhibit T cell glycolysis in prostate cancer microenvironment by SHP1/PKM2/LDHB axis DOI Creative Commons
Lei Chang,

Guohao Li,

Shan Jiang

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Feb. 8, 2024

Abstract Background Our previous studies demonstrated that 1-Pyrroline-5-carboxylate (P5C) released by prostate cancer cells inhibits T cell proliferation and function increasing SHP1 expression. We designed this study to further explore the influence of P5C on metabolism, produced an antibody for targeting restore functions cells. Method co-immunoprecipated from analyzed proteins were bound it using liquid chromatography mass spectrometry (LC/MS-MS). The metabolism was also detected LC/MS-MS. Seahorse XF96 analyzer used identify effect glycolysis. subsequently monoclonal technique verified its effectiveness in vitro vivo. Result PKM2 LDHB bind cells, could increase levels p-PKM2 while having no LDHB. found influences energy carbohydrate metabolism. activity decreases content intracellular lactic acid LDH. Using seahorse analyzer, we confirmed remarkably glycolysis oppose process Meanwhile, growth tumors animal model. Conclusion revealed SHP1/PKM2/LDHB complexes. Moreover, is important inhibit tumors.

Language: Английский

Metabolic challenges and interventions in CAR T cell therapy DOI
Jhan-Jie Peng, Limei Wang, Zhiyu Li

et al.

Science Immunology, Journal Year: 2023, Volume and Issue: 8(82)

Published: April 14, 2023

Chimeric antigen receptor (CAR) T cells have achieved true clinical success in treating hematological malignancy patients, laying the foundation of CAR as a new pillar cancer therapy. Although these promising effects generated strong interest expanding treatment to solid tumors, reproducible demonstration efficacy setting tumors has remained challenging date. Here, we review how metabolic stress and signaling tumor microenvironment, including intrinsic determinants response cell therapy extrinsic obstacles, restrict treatment. In addition, discuss use novel approaches target rewire programming for manufacturing. Last, summarize strategies that aim improve adaptability enhance their potency mounting antitumor responses survival within microenvironment.

Language: Английский

Citations

59

Cold and hot tumors: from molecular mechanisms to targeted therapy DOI Creative Commons
Bo Wu, Bo Zhang, Bowen Li

et al.

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

Published: Oct. 18, 2024

Immunotherapy has made significant strides in cancer treatment, particularly through immune checkpoint blockade (ICB), which shown notable clinical benefits across various tumor types. Despite the transformative impact of ICB treatment therapy, only a minority patients exhibit positive response to it. In with solid tumors, those who respond well typically demonstrate an active profile referred as "hot" (immune-inflamed) phenotype. On other hand, non-responsive may distinct "cold" (immune-desert) phenotype, differing from features tumors. Additionally, there is more nuanced "excluded" positioned between and categories, known type. Effective differentiation understanding intrinsic factors, characteristics, TME, external factors are critical for predicting results. It widely accepted that therapy exerts profound effect on limited efficacy against or "altered" necessitating combinations therapeutic modalities enhance cell infiltration into tissue convert tumors ones. Therefore, aligning traits this review systematically delineates respective influencing extensively discusses varied approaches drug targets based assess efficacy.

Language: Английский

Citations

39

100 years of the Warburg effect: A cancer metabolism endeavor DOI
Sarah‐Maria Fendt

Cell, Journal Year: 2024, Volume and Issue: 187(15), P. 3824 - 3828

Published: July 1, 2024

Language: Английский

Citations

30

Prospects and challenges of CAR-T cell therapy combined with ICIs DOI Creative Commons

Yufan Lv,

Xinyu Luo,

Zhuoyi Xie

et al.

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: March 20, 2024

Immune checkpoint molecules are a group of expressed on the surface immune cells that primarily regulate their homeostasis. Chimeric antigen receptor (CAR) T cell therapy is an immunotherapeutic technology realizes tumor-targeted killing by constructing synthetic expressing specific antigens through biotechnology. Currently, CAR-T has achieved good efficacy in non-solid tumors, but its treatment solid tumors not yielded desired results. inhibitors (ICIs) combined with novel combination high expectations to defeat tumors. This review addresses challenges and this

Language: Английский

Citations

17

The role of microRNAs in the gastric cancer tumor microenvironment DOI Creative Commons
Xianzhe Yu,

Yin Zhang,

Fengming Luo

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Aug. 20, 2024

Gastric cancer (GC) is one of the deadliest malignant tumors with unknown pathogenesis. Due to its treatment resistance, high recurrence rate, and lack reliable early detection techniques, a majority patients have poor prognosis. Therefore, identifying new tumor biomarkers therapeutic targets essential. This review aims provide fresh insights into enhancing prognosis GC by summarizing processes through which microRNAs (miRNAs) regulate microenvironment (TME) highlighting their critical role in TME. A comprehensive literature was conducted focusing on interactions among cells, extracellular matrix, blood vessels, cancer-associated fibroblasts, immune cells within The noncoding RNAs, known as miRNAs, modulating TME various signaling pathways, cytokines, growth factors, exosomes specifically examined. Tumor formation, metastasis, therapy are significantly influenced miRNAs progression these multiple exosomes. Dysregulation affects cellular such cell proliferation, differentiation, angiogenesis, contributing pathogenesis GC. play crucial regulation TME, influencing patient By understanding mechanisms control potential can be identified improve

Language: Английский

Citations

17

MAZ-mediated tumor progression and immune evasion in hormone receptor-positive breast cancer: Targeting tumor microenvironment and PCLAF+ subtype-specific therapy DOI
Gaofeng Ni,

Yuwei Sun,

Hongling Jia

et al.

Translational Oncology, Journal Year: 2025, Volume and Issue: 52, P. 102280 - 102280

Published: Jan. 13, 2025

Language: Английский

Citations

5

Spatial and Single-Cell Transcriptomics Reveal a Cancer-Associated Fibroblast Subset in HNSCC That Restricts Infiltration and Antitumor Activity of CD8+ T Cells DOI Creative Commons
Chuwen Li, Haiyan Guo,

Peisong Zhai

et al.

Cancer Research, Journal Year: 2023, Volume and Issue: 84(2), P. 258 - 275

Published: Nov. 6, 2023

Abstract Although immunotherapy can prolong survival in some patients with head and neck squamous cell carcinoma (HNSCC), the response rate remains low. Clarification of critical mechanisms regulating CD8+ T-cell infiltration dysfunction tumor microenvironment could help maximize benefit for treating HNSCC. Here, we performed spatial transcriptomic analysis HNSCC specimens differing immune single-cell RNA sequencing five pairs adjacent tissues, revealing specific cancer-associated fibroblast (CAF) subsets related to restriction dysfunction. These CAFs exhibited high expression CXCLs (CXCL9, CXCL10, CXCL12) MHC-I enrichment galectin-9 (Gal9). The proportion MHC-IhiGal9+ was inversely correlated abundance a TCF1+GZMK+ subset T cells. Gal9 on induced decreased tumor-infiltrating TCF1+CD8+ Collectively, identification advances understanding precise role cancer evasion paves way more effective Significance: Spatial identifies IFN-induced that form trap cells, providing insights into complex networks regulate function.

Language: Английский

Citations

31

The screening, identification, design and clinical application of tumor-specific neoantigens for TCR-T cells DOI Creative Commons
Jianping Li, Zhiwen Xiao,

Donghui Wang

et al.

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Aug. 30, 2023

Recent advances in neoantigen research have accelerated the development of tumor immunotherapies, including adoptive cell therapies (ACTs), cancer vaccines and antibody-based therapies, particularly for solid tumors. With next-generation sequencing bioinformatics technology, rapid identification prediction tumor-specific antigens (TSAs) has become possible. Compared with tumor-associated (TAAs), highly immunogenic TSAs provide new targets personalized immunotherapy can be used as prospective indicators predicting patient survival, prognosis, immune checkpoint blockade response. Here, characterization neoantigens clinical application neoantigen-based TCR-T strategies are summarized, current status, inherent challenges, translational potential these discussed.

Language: Английский

Citations

29

The multifaceted roles of GSDME-mediated pyroptosis in cancer: therapeutic strategies and persisting obstacles DOI Creative Commons
Yixiang Hu, Ya Liu,

Lijuan Zong

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(12)

Published: Dec. 16, 2023

Abstract Pyroptosis is a novel regulated cell death (RCD) mode associated with inflammation and innate immunity. Gasdermin E (GSDME), crucial component of the gasdermin (GSDM) family proteins, has ability to convert caspase-3-mediated apoptosis pyroptosis cancer cells activate anti-tumor Accumulating evidence indicates that GSDME methylation holds tremendous potential as biomarker for early detection, diagnosis, prognosis, treatment tumors. In fact, GSDME-mediated performs dual role in therapy. On one side, pyroptotic tumors caused by contributes inflammatory cytokines release, which transform tumor immune microenvironment (TIME) from ‘cold’ ‘hot’ state significantly improve immunotherapy. However, due expressed nearly all body tissues cells, it can exacerbate chemotherapy toxicity partially block response. How achieve balance between two sides research topic. Meanwhile, functions anti-programmed protein 1 (PD-1) therapy, antibody-drug conjugates (ADCs) chimeric antigen receptor T (CAR-T cells) therapy have not yet been fully understood, how clinical outcomes persists obscure. this review, we systematically summarize latest regarding molecular mechanisms discuss immunity its applications treatment.

Language: Английский

Citations

23

Immunometabolism of CD8+ T cell differentiation in cancer DOI
Hao Shi, Sidi Chen, Hongbo Chi

et al.

Trends in cancer, Journal Year: 2024, Volume and Issue: 10(7), P. 610 - 626

Published: April 30, 2024

Language: Английский

Citations

15