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PD-L2 based immune signature confers poor prognosis in HNSCC.

ABSTRACT: PD-L2 expression is an important predictor of anti-PD-1 therapy efficacy in patients with head and neck squamous cell carcinoma (HNSCC). However, whether the PD-L2-based immune signature can serve as a prognostic biomarker for patients with HNSCC remains unclear. Here, we reported that PD-L2 was positively stained in 62.7% of tumors, which was more than twice as that of PD-L1, and in 61.4% of patients with PD-L1-negative tumors. Survival tree analysis (STA) revealed that PD-L2^high was an independent predictor of poor overall survival (OS). Six patterns were generated from STA, demonstrating that patients with PD-L2^lowCD3^high were associated with an improved median OS of 72 months and prognostic index (PI) of -3.95 (95% CI, -5.14 to -2.76), whereas patients with PD-L2^highCD3^lowCD8^low to a median OS of 10 months and PI of 1.43 (95% CI, 0.56 to 2.30). Analysis of single-cell RNA sequencing showed that PD-L2 expression was associated with IL-6 expression. We confirmed that IL-6 augments PD-L2 expression in HNSCC cell lines. The PD-L2-based immune signature can serve as an effective biomarker for anti-PD-1 therapy. In addition, PD-L2 may serve as a potential immunotherapeutic target, and we propose anti-IL6 therapy in the adjuvant setting for patients with HNSCC with high PD-L2 expression.

SUBMITTER: Qiao Y

PROVIDER: S-EPMC8344752 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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PD-L2 based immune signature confers poor prognosis in HNSCC.

Qiao Yu Y Liu Chao C Zhang Xiaoyue X Zhou Qianqian Q Li Yatian Y Xu Yini Y Gao Zhenyue Z Xu Yiqi Y Kong Lingping L Yang Aifeng A Mei Mei M Ren Yu Y Wang Xudong X Zhou Xuan X

Oncoimmunology 20210804 1

PD-L2 expression is an important predictor of anti-PD-1 therapy efficacy in patients with head and neck squamous cell carcinoma (HNSCC). However, whether the PD-L2-based immune signature can serve as a prognostic biomarker for patients with HNSCC remains unclear. Here, we reported that PD-L2 was positively stained in 62.7% of tumors, which was more than twice as that of PD-L1, and in 61.4% of patients with PD-L1-negative tumors. Survival tree analysis (STA) revealed that PD-L2<sup>high</sup> was ...[more]

PMID: 34377590

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Project description:BackgroundProgrammed cell death protein 1 (PD-1) is a key immune checkpoint that regulates peripheral tolerance and protects against autoimmunity. Programmed death ligand-2 (PD-L2) is a less studied ligand to PD-1 and has yet to be fully explored, especially in pancreatic ductal adenocarcinoma (PDAC).MethodsIn this study, we performed immunohistochemistry to detect the PD-L2, CD3, CD8, transforming growth factor-β2 (TGF-β2) and FOXP3 levels in paraffin sections from 305 patients with resected PDAC as a training set. Expression levels of intratumoral and stromal immune markers were compared in relation to survival using Kaplan-Meier curves, random survival forest model and survival tree analysis. A multivariable Cox proportional-hazards model of associated markers was used to calculate the risk scores.ResultsPD-L2 was expressed in 71.5% of PDAC samples and showed strong correlations with CD3+, CD8+ T cells and FOXP3+ regulatory T cell densities. High levels of intratumoral PD-L2 and FOXP3 were related to poor survival; only stromal FOXP3 overexpression was associated with worse prognosis. Four patterns generated from survival tree analysis demonstrated that PD-L2lowstromalFOXP3low patients had the longest survival, while PD-L2highintratumoralCD3low patients had the shortest survival (P < 0.001). The area under the curve was 0.631(95% confidence interval (CI): 0.447-0.826) for the immune marker-based signature and 0.549 (95% CI: 0.323-0.829; P < 0.001) for the clinical parameter-based signature, which was consistent with the results in the validation set including 150 patients (P < 0.001). A higher risk score indicated shorter survival and could serve as an independent prognostic factor. PD-L2 was also showed associated with TGF-β2 and other immune molecules based on bioinformatics analysis.ConclusionsOur work highlighted PD-L2 as a promising immunotherapeutic target with prognostic value combined with complex tumor infiltrating cells in PDAC.

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PD-L2 based immune signature confers poor prognosis in HNSCC.

Publications

PD-L2 based immune signature confers poor prognosis in HNSCC.

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