Journal
ANIMAL MODELS AND EXPERIMENTAL MEDICINE
Volume -, Issue -, Pages -Publisher
WILEY
DOI: 10.1002/ame2.12355
Keywords
Chinese patients; ICOS; ICOSL; lung adenocarcinoma; prognostic factor
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ICOS/ICOSL may be associated with the prognosis of lung cancer and could serve as potential therapeutic targets in non-small cell lung cancer. This study analyzed the expression of ICOS and ICOSL in lung tumor tissues and found that their expression levels were correlated with patient survival.
BackgroundImmunotherapy has become the fastest-adopting treatment paradigm for lung cancer with improved survival. By binding with its ligand (inducible T-cell co-stimulator and its ligand [ICOSL]), an inducible T-cell co-stimulator (ICOS) could contribute to reversing immunosuppression and improving immune response and thus be a potential target for cancer immunotherapy.MethodsWe selected 54 formalin-fixed, paraffin-embedded tumor tissues from cases with stage I-III lung adenocarcinoma cancer. Immunohistochemical expression of ICOS and ICOSL was evaluated. The correlation with clinical parameters in Chinese patients was also compared with TCGA results.ResultsThe positive rates of ICOS and ICOSL were 68% and 81.5%, respectively, in lung tumor tissues. Of these, 9 cases had a low expression of ICOS, and 22 cases had a high expression of ICOS; ICOSL expression was low in 20 cases and high in 24 cases. According to the International Association for the Study of Lung Cancer (8th edition), phase I lesions were detected in 21 cases, phase II lesions in 15 cases, and phase III lesions in 18 cases. The median survival time of all patients was 44.5 months, and the median disease-free survival was 32 months. Univariate analysis showed that the factors significantly associated with overall survival were tumor size, regional lymph node involvement, stage, and expression level of ICOS/ICOSL. Survival analysis using log-rank test indicated that the lower ICOS+ cell infiltration may predict poor prognosis, whereas lower ICOSL protein expression may be associated with better prognosis, but ICOSL data need further validation in larger samples due to inconsistency in TCGA mRNA prediction.ConclusionICOS/ICOSL might be associated with prognosis of lung cancer, and ICOS and its ligand may be potential therapeutic targets in non-small cell lung cancer. This study included the data of patients who were diagnosed with adenocarcinoma by pathology after initial treatment and radical operation in Beijing Chaoyang Hospital from October 2016 to January 2018. The relevant medical records of patients were collected and sorted out according to the demographic, clinical, and pathological features, curative treatment effect evaluation, and long-term survival after treatment. Immunohistochemical analyses were performed according to methods published by Budwit-Novotny et al. The expression of T-cell co-stimulator and inducible T-cell co-stimulator and its ligand were divided to negative, low and high.image
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