Unlocking the potential of HHLA2: identifying functional immune infiltrating cells in the tumor microenvironment and predicting clinical outcomes in laryngeal squamous cell carcinoma

• DOI: 10.1007/s00262-024-03791-6
• Publication Date: 2024-08-06T13:08:23Z
• Authors: Wenjing Li; Jianqing You; Haixiang Xue; Yi Liu; Junjun Chen; Xiao Zheng; Lujun Chen; Changping Wu
• Keywords: Pathogenesis; Clinical Significance

HHLA2 (human endogenous retrovirus-H long terminal repeat-associating protein 2) represents a recently identified member of the B7 immune checkpoint family, characterized by limited expression in normal tissues but notable overexpression various cancer types. Nevertheless, precise function and interaction with cells remain poorly understood, particularly laryngeal squamous cell carcinoma (LSCC). This investigation endeavored to elucidate biological significance within tumor microenvironment human LSCC delineate clinical relevance functional roles pathogenesis. Through multiplexed immunohistochemistry analyses conducted on tissue microarrays sourced from patients (n = 72), analysis was executed assess levels HHLA2, density spatial patterns CD68+HLA-DR+CD163− (M1 macrophages), CTLA-4+CD4+FoxP3+ (CTLA-4+Treg cells), CTLA-4+CD4+FoxP3− (CTLA-4+Tcon exhausted CD8+T cells, terminally tissues. Survival evaluate prognostic these checkpoints or populations, employing COX regression identify independent factors. Kaplan–Meier (K–M) survival curves revealed significant association between overall (OS) LSCC. Elevated were linked reduced patient survival, indicating its potential as marker (HR: 3.230, 95%CI 0.9205–11.34, P 0.0067). Notably, increased infiltration CD68+ (total STING+CD68+HLA-DR+CD163− (STING+M1 CTLA-4+CD4+FoxP3+, CTLA-4+CD4+FoxP3−, PD-1+LAG-3+CD8+T PD-1+LAG-3+TIM-3+CD8+T strongly poorer outcomes (P < 0.05). A discernible trend observed STING+CD68+ (STING+ total CD68+HLA-DR+CD163−, STING+CD68+CD163+HLA-DR− (STING+M2 PD-1+LAG-3−CD8+T PD-1+TIM-3+CD8+T PD-1+LAG-3+TIM-3−CD8+T prognosis. Importantly, multivariate an predictive factor for OS (HR 3.86, 95% CI 1.08–13.80, 0.038). underscored critical predicting emerged detrimental biomarker assessing patients. Relative other checkpoints, exhibited heightened efficacy prognosis