LAG-3 expression on tumor-infiltrating T cells in soft tissue sarcoma correlates with poor survival

Que, Yi; Fang, Zhang; Guan, Yuanxiang; Xiao, Wei; Xu, Bu-Shu; Zhao, Jingjing; Chen, Huoying; Zhang, Xinke; Zeng, Mu‐Sheng; Liang, Yao; Xing, Zhou

doi:10.20892/j.issn.2095-3941.2018.0306

Cited by 42 publications

(14 citation statements)

References 40 publications

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“…In some cases, LAG3 can be found in a soluble form (sLAG3) [ 44 ]. In a study carried out on 163 STS-affected patients, it was found that the frequency of CD8 + and CD4 + T lymphocytes expressing LAG3 is higher than in healthy controls; moreover, the expression is correlated with the presence of TILs CD8 + , with a severe prognosis and advanced tumor stage [ 45 ]. LAG3 is often co-expressed with PD1, and rarely with TIM3 [ 33 ].…”

Section: Molecular Markers Associated With Prognosismentioning

confidence: 99%

Soft Tissue Sarcoma: An Insight on Biomarkers at Molecular, Metabolic and Cellular Level

Pillozzi

Bernini

Palchetti

et al. 2021

Cancers

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Soft tissue sarcomas (STSs) are a heterogeneous group of rare tumors. Although constituting only 1% of all human malignancies, STSs represent the second most common type of solid tumors in children and adolescents and comprise an important group of secondary malignancies. Over 100 histologic subtypes have been characterized to date (occurring predominantly in the trunk, extremity, and retroperitoneum), and many more are being discovered due to molecular profiling. STS mortality remains high, despite adjuvant chemotherapy. New prognostic stratification markers are needed to help identify patients at risk of recurrence and possibly apply more intensive or novel treatments. Recent scientific advancements have enabled a more precise molecular characterization of sarcoma subtypes and revealed novel therapeutic targets and prognostic/predictive biomarkers. This review aims at providing a comprehensive overview of the most relevant cellular, molecular and metabolic biomarkers for STS, and highlight advances in STS-related biomarker research.

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Section: Molecular Markers Associated With Prognosismentioning

confidence: 99%

Soft Tissue Sarcoma: An Insight on Biomarkers at Molecular, Metabolic and Cellular Level

Pillozzi

Bernini

Palchetti

et al. 2021

Cancers

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“…The expression and function of LAG-3 in the TME was investigated in glioblastoma by Harris-Bookman and co-workers [ 167 ], who demonstrated its expression mainly in TIL. Moreover, they setup an orthotopic preclinical model of glioblastoma and observed that combined therapy using anti-LAG-3 and anti-PD-1 antibodies was more effective in terms of increased overall survival than the single therapy.…”

Section: Ic As Immunotherapeutic Targets In Pediatric Solid Cancersmentioning

confidence: 99%

“…TIGIT is a cell surface protein identified by bioinformatics analysis of the genes expressed in activated T cells. TIGIT is composed of a single Ig domain, a type I trans-membrane domain and a single intracellular immune-receptor tyrosine-based in- The expression and function of LAG-3 in the TME was investigated in glioblastoma by Harris-Bookman and co-workers [167], who demonstrated its expression mainly in TIL. Moreover, they setup an orthotopic preclinical model of glioblastoma and observed that combined therapy using anti-LAG-3 and anti-PD-1 antibodies was more effective in terms of increased overall survival than the single therapy.…”

Section: Tigitmentioning

confidence: 99%

Immune Checkpoints in Pediatric Solid Tumors: Targetable Pathways for Advanced Therapeutic Purposes

Cocco¹,

Morandi²,

Airoldi³

2021

Cells

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The tumor microenvironment (TME) represents a complex network between tumor cells and a variety of components including immune, stromal and vascular endothelial cells as well as the extracellular matrix. A wide panel of signals and interactions here take place, resulting in a bi-directional modulation of cellular functions. Many stimuli, on one hand, induce tumor growth and the spread of metastatic cells and, on the other hand, contribute to the establishment of an immunosuppressive environment. The latter feature is achieved by soothing immune effector cells, mainly cytotoxic T lymphocytes and B and NK cells, and/or through expansion of regulatory cell populations, including regulatory T and B cells, tumor-associated macrophages and myeloid-derived suppressor cells. In this context, immune checkpoints (IC) are key players in the control of T cell activation and anti-cancer activities, leading to the inhibition of tumor cell lysis and of pro-inflammatory cytokine production. Thus, these pathways represent promising targets for the development of effective and innovative therapies both in adults and children. Here, we address the role of different cell populations homing the TME and of well-known and recently characterized IC in the context of pediatric solid tumors. We also discuss preclinical and clinical data available using IC inhibitors alone, in combination with each other or administered with standard therapies.

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“…Specifically, the expression of LAG-3 on tumor infiltrating lymphocytes (17), natural killer cells (18), B cells (19) and dendritic cells (20) indicates its involvement in a widespread and complex immune pathways. LAG-3 is evaluated in various types of cancer (21)(22)(23) and has a synergistic effect with PD-1/PD-L1 axis (24)(25)(26). According to our recent study, high expression of LAG-3 in tumor tissue indicated an unfavorable prognosis in HCC (27).…”

Section: Introductionmentioning

confidence: 99%

Serum LAG-3 Predicts Outcome and Treatment Response in Hepatocellular Carcinoma Patients With Transarterial Chemoembolization

et al. 2021

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BackgroundTransarterial chemoembolization (TACE) stands for the most commonly utilized therapy for hepatocellular carcinoma (HCC) worldwide. This study was to explore the potential predictive and prognostic roles of LAG-3 and PD-L1 as serum biomarkers in HCC patients underwent TACE treatment.MethodsA total of 100 HCC patients receiving TACE as well as 30 healthy controls were enrolled in the study. Serum LAG-3 and PD-L1 levels were determined at baseline and 3 day after TACE using enzyme-linked immunosorbent assay (ELISA).ResultsWe found serum levels of LAG-3 and PD-L1 were significantly elevated in HCC patients compared with healthy controls. Interestingly, patients with low pre-TACE and post-TACE levels of LAG-3 but not PD-L1 had a high probability of achieving an objective response (OR) after TACE treatment. Additionally, high pre-TACE LAG-3 level was correlated with poor disease outcome, and the patients with both high serum LAG-3 and PD-L1 level had the shorter overall survival (OS) than patients who are either PD-L1 or LAG-3 high or both PD-L1 and LAG-3 low. High pre-TACE serum LAG-3 level was positively associated with more cirrhosis pattern, advanced BCLC stage, pre-TACE alanine aminotransferase (ALT) level, and pre-TACE aspartate aminotransferase (AST) level. Furthermore, in 50 patients who underwent TACE, the serum LAG-3 level was significantly decreased at 3 day after TACE.ConclusionBoth pre-TACE and post-TACE serum LAG-3 levels could serve as powerful predictors for tumor response of TACE, and high pre-TACE serum LAG-3 level was an indicator for poor prognosis in HCC.

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LAG-3 expression on tumor-infiltrating T cells in soft tissue sarcoma correlates with poor survival

Cited by 42 publications

References 40 publications

Soft Tissue Sarcoma: An Insight on Biomarkers at Molecular, Metabolic and Cellular Level

Soft Tissue Sarcoma: An Insight on Biomarkers at Molecular, Metabolic and Cellular Level

Immune Checkpoints in Pediatric Solid Tumors: Targetable Pathways for Advanced Therapeutic Purposes

Serum LAG-3 Predicts Outcome and Treatment Response in Hepatocellular Carcinoma Patients With Transarterial Chemoembolization

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