ArticleCancer immunology, immunotherapy : CII2024
Expression patterns of novel immunotherapy targets in intermediate- and high-grade lung neuroendocrine neoplasms.
Article in Cancer immunology, immunotherapy : CII, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 1 citations in OpenAlex.
- Role and clinical significance of VISTA (PD-1H) and PVR (CD155) expression in non-small cell lung carcinoma: a systematic review.Translational lung cancer research · 2026Review
- Near Infrared Photoimmunotherapy for Lung Cancer: Recent Development and Perspective.ImmunoTargets and therapy · 2026Review
- Recent advances in preclinical studies combining hyperthermia therapy with novel immune checkpoint targeting agents.Frontiers in immunology · 2026Review
- [Research Progress on Molecular Subtypes and Precision Therapy of Pulmonary Large Cell Neuroendocrine Carcinoma].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Review
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Authors and funding
22 authors at 6 institutions in 4 countries.
Funding
Abstract
backgroundAdvancements in immunotherapeutic approaches only had a modest impact on the therapy of lung neuroendocrine neoplasms (LNENs). Our multicenter study aimed to investigate the expression patterns of novel immunotherapy targets in intermediate- and high-grade LNENs.
methodsThe expressions of V-domain Ig suppressor of T cell activation (VISTA), OX40L, Glucocorticoid-induced TNF receptor (GITR), and T cell immunoglobulin and mucin domain 3 (TIM3) proteins were measured by immunohistochemistry in surgically resected tumor samples of 26 atypical carcinoid (AC), 49 large cell neuroendocrine lung cancer (LCNEC), and 66 small cell lung cancer (SCLC) patients. Tumor and immune cells were separately scored.
resultsTumor cell TIM3 expression was the highest in ACs (p < 0.001), whereas elevated tumor cell GITR levels were characteristic for both ACs and SCLCs (p < 0.001 and p = 0.011, respectively). OX40L expression of tumor cells was considerably lower in ACs (vs. SCLCs; p < 0.001). Tumor cell VISTA expression was consistently low in LNENs, with no significant differences across histological subtypes. ACs were the least immunogenic tumors concerning immune cell abundance (p < 0.001). Immune cell VISTA and GITR expressions were also significantly lower in these intermediate-grade malignancies than in SCLCs or in LCNECs. Immune cell TIM3 and GITR expressions were associated with borderline prognostic significance in our multivariate model (p = 0.057 and p = 0.071, respectively).
conclusionsLNEN subtypes have characteristic and widely divergent VISTA, OX40L, GITR, and TIM3 protein expressions. By shedding light on the different expression patterns of these immunotherapy targets, the current multicenter study provides support for the future implementation of novel immunotherapeutic approaches.
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