Esophageal squamous cell carcinoma (ESCC) is a malignant epithelial tumor with a high incidence in East Asia and the Middle East. The outcomes for ESCC patients are usually not optimal due to the recurrence and metastasis. This study is aim to examine the expression and the prognostic value of LAG-3 in ESCC. We applied immunohistochemistry analysis to examine the expression of LAG-3, CD4 and CD8 in 287 ESCC cohorts. Our study demonstrated that the decreased LAG-3 expression was significantly associated with CD4 tumor-infiltrated lymphocytes (TILs) (=0.000), CD8 TILs (=0.000), and the advanced clinical stages (=0.041) by Chi-square analysis. Kaplan-Meier survival analysis revealed that higher LAG-3 expression were positively correlated with a better overall survival (OS) (=0.010) and better progression free survival (PFS) (=0.006), especially in the patients at stages T1-2 status (=0.001, OS; =0.001, PFS), N0 status (=0.036, OS; =0.050, PFS), and early stages (I-II) (=0.006, OS; =0.008, PFS). Both high of CD4 TIL /CD8 TIL ratio and LAG-3 expression were correlated with longer OS and PFS. Cox proportional hazards regression analysis showed that LAG-3 is an independent biomarker of survival (HR, 0.724; 95% CI 0.526-0.995; = 0.047) (=0.036). Taken together, we found that high expression of LAG-3 was correlated with an improved survival and LAG-3 is an independent predictor of survival, suggesting that LAG-3 may serve as a useful immune marker for the prognosis of ESCC.
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http://dx.doi.org/10.7150/jca.26949 | DOI Listing |
NPJ Genom Med
March 2025
Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin Cancer Center, Milwaukee, WI, USA.
Programmed cell death protein 1 (PD-1) is a critical immune checkpoint receptor and a target for cancer immune checkpoint inhibitors (ICI). We investigated PD-1 transcript expression across cancer types and its correlations to clinical outcomes. Using a reference population, PD-1 expression was calculated as percentiles in 489 of 514 patients (31 cancer types) with advanced/metastatic disease.
View Article and Find Full Text PDFCommun Biol
March 2025
Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI, USA.
The nature of the effector and memory T cell response in the lungs following acute SARS-CoV-2 infections remains largely unknown. To define the pulmonary T-cell response to COVID-19, we compared effector and memory T-cell responses to SARS-CoV-2 and influenza A virus (IAV) in mice. Both viruses elicited potent effector T cell responses in lungs, but memory T cells showed exaggerated contraction in SARS-CoV-2-infected mice.
View Article and Find Full Text PDFClin Transl Oncol
February 2025
Department of Pathology, University of Health Sciences Prof. Dr. Cemil Taşcıoğlu City Hospital, İstanbul, Turkey.
J Immunother Cancer
February 2025
Bristol Myers Squibb, Princeton, New Jersey, USA.
Background: Some patients with melanoma experience disease progression during immunotherapy (IO) and may benefit from novel combinations of immune checkpoint inhibitors (ICIs). We report results from exploratory biomarker analyses to characterize the responses of patients with advanced melanoma to treatment with nivolumab (anti-programmed cell death-1 (PD-1)) and relatlimab (anti-lymphocyte-activation gene 3 (LAG-3)) combination therapy in RELATIVITY-020 (NCT01968109).
Methods: Tumor biopsies collected at baseline and ≤4 weeks after treatment initiation were evaluated for % LAG-3-positive and % CD8-positive immune cells and % programmed death-ligand 1 (PD-L1) expression on tumor cells.
Front Immunol
February 2025
Immunology Discovery Research, Lilly Research Laboratories, Lilly Biotechnology Center, San Diego, CA, United States.
Introduction: We investigated the impact of rheumatoid arthritis (RA) associated cytokines and standard of care (SOC) RA therapeutics on immune checkpoint receptor (IR) expression on T cells to gain insights to disease pathology and therapeutic avenues.
Methods: We assessed IR expression by flow cytometry on T cell receptor activated T cells cultured in the presence of exogenously added single cytokines or RA patient synovial fluid. We also assessed RA synovial fluid stimulated samples in the presence of various single cytokine neutralizing antibodies or SOC therapeutics, including glucocorticoids, TNF, IL-6 receptor and JAK inhibitors.
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