Immune biomarkers in thymic epithelial tumors: expression patterns, prognostic value and comparison of diagnostic tests for PD-L1

Background2-Deoxy-2-[fluorine-18]-fluoro-d-glucose (18F-FDG) positron emission tomography (18F-FDG-PET) is a convenient modality to assess metabolic activity within tumor cells. However, there is no consensus regarding the relationship between 18F-FDG uptake and the immune environment in thymic epithelial tumors (TETs). We conducted a clinicopathological study to elucidate the relationship between 18F-FDG uptake and programmed death ligands 1 and 2 (PD-L1/PD-L2) expression in patients with TETs. MethodsA total of 108 patients with histologically confirmed TETs classified as thymomas or thymic carcinomas who underwent surgical resection or biopsy or needle biopsy and 18F-FDG PET before any treatment between August 2007 and March 2020 were enrolled in this study. Tumor specimens underwent immunohistochemical staining for PD-L1, PD-L2, GLUT1, HIF-1α, VEGFR2, VEGF-C and β2 adrenergic receptor. ResultsHigh uptakes of SUVmax, SUVmean, MTV and TLG were identified in 28 (25.9%), 61 (56.5%), 55 (50.9%) and 55 (50.9%) of 108 patients, respectively. High uptake of SUVmax significantly correlated with PS of 1-2, thymic carcinoma and advanced stage, and SUVmax on 18F-FDG uptake displayed a close association with PD-L1 and PD-L2 expression, but not MTV and TLG. Multivariate analysis revealed that SUVmax was identified as an independent predictor for positive PD-L1 /PD-L2 expression. GLUT1 was clarified as a significant marker for the expression of PD-L1/PD-L2 from the biological viewpoint. Conclusion18F-FDG accumulation was closely associated with the expression of PD-L1/PD-L2, which, in turn, was correlated with glucose metabolism and hypoxia. PD-L1/PD-L2 could affect glucose metabolism and hypoxia in thymic tumor cells.

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“…Although we also performed PD-L2 staining using the same antibody, no staining was observed in our study, corresponding to their results 19 .…”

Section: Discussionsupporting

confidence: 82%

“…However, little is known about the clinicopathological signi cance of PD-L2 expression in patients with TETs. Recently, Rouquette et al reported that the PD-L2 antibody stained no tumor epithelial cells in TETs 19 .…”

Section: Discussionmentioning

confidence: 99%

Tumor Immunity is Related to 18F-FDG Uptake in Thymic Epithelial Tumor

Imai

Kaira

Hashimoto

et al. 2020

Preprint

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“…Also, superior vena cava thrombosis in 6.6 % of patients while pneumonia in 6.6 % of patients. However, thromboembolism of small pulmonary arteries in 6.6 % of patients [3,10].…”

Section: Discussionmentioning

confidence: 99%

“…The superior vena cava syndrome (SVCS) was first described in 1757 [1,2]. Reduced blood flow in the superior vena cava (SVC) system decreases the amount of venous blood in the right auricle, causing a number of clinical characteristics and symptoms, such as dilated neck veins, oedematous upper limbs, cyanosis, headache, dyspnoea, cough, and dysphagia [3,4]. Impaired blood flow may be caused by external compression, direct tumour invasion, thrombosis, or ineffective venous return as a consequence of diseases affecting the right auricle or the vessel lumen itself.…”

Section: Introductionmentioning

confidence: 99%

Outcomes of surgical reconstruction of the superior vena cava syndrome in patients with locally advanced thymomas

et al. 2021

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The aim of the study: to study and demonstrate the potential and technical aspects of the surgical treatment of locally advanced thymus tumours with the tumour infiltrate affecting superior vena cava and its branches. Methods. 56 patients with locally advanced thymomas complicated by SVCS were study. The control group included 30 patients with SVCS were treated with conventional techniques, while the experimental group included 26 patients who underwent a novel bypass surgery developed by us. Results. Based on our observations, patients tolerated these surgeries much better. The venous bypass was mandatorily complemented with cytoreduction. Auriculo-jugular (left and right) and auriculo-subclavian (left and right) bypasses were used in our observations Complications in the post-operative period were reported from the experimental group and included auriculo-subclavian bypass thrombosis, post-operative complications were reported in the control group including haemorrhage from the sternotomy wound in 1 (3.3 %) case, superior vena cava thrombosis in 2 (6.6 %) cases, pneumonia in 2 (6.6 %) cases and thromboembolism of small pulmonary arteries in 2 (6.6 %) cases. Post-operative lethality in the study groups was reported in the control and in the experimental group. Total lethality rate was 8.9 % (5 patients). The relative risk of complications and lethal outcome was calculated for patients from both groups. It was found that the risk of complications was twice as high in the control group as in the experimental group (standard error of relative risk equals 0.64), whereas the risk of lethal outcome increased by a factor of 3.5 in the control group (standard error of relative risk equals 1.09) Conclusion. It has been established that the superior vena cava syndrome in patients with locally advanced thymoma is an emergency condition whose surgical correction must be personalised depending on the anatomic and topographic classification of SVC lesion types. It is known that an obligatory pre-condition of the perioperative period in this category of patients is an adequate vascular approach to the superior vena cava system. The first mandatory step of the radical surgery in patients with locally advanced thymomas with SVC invasion should be the auriculo-jugular and auriculo-subclavian bypasses, which can reduce the relative risk of post-operative complications by a factor of the risk of lethal by a factor of 3.5.

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“…In this study, the PD-L2 expression was positive in 41 patients (58.6%). However, Isabelle Rouquette et al found that PD-L2 antibody stained no thymic epithelial tumors [15] . Different antibody and cutoff values vary among studies.…”

Section: Discussionmentioning

confidence: 99%

The expression of Programmed death ligand 2 in patients with thymoma and thymomatous Myasthenia Gravis

Zhu

Zhang

Wang

et al. 2020

Preprint

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Background There is a growing relationship between PD-1/PD-Ls and autoimmune disease We attempted to explore the relationship of the PD-L2 expression in patients with thymoma, especially with Myasthenia Gravis (thymomatous MG).Methods Seventy patients with thymoma who underwent surgical resection between January 2017 to December 2018 were retrospectively reviewed. The PD-L2 expression was evaluated by immunohistochemistry. The association between the PD-L2 expression and the clinicopathologic features was investigated, especially thymomatous MG. Results The PD-L2 expression was positive in 41 patients (58.6%) and negative in 29 patients (41.4%). The PD-L2 expression was significantly associated with WHO histology of type B2 and B3 thymoma (p=0.008) and the status of MG (p=0.002). In addition, PD-L2 positive tumors showed a significantly smaller tumor size (P=0.017). Ectopic thymus was significantly more often seen in the PD-L2 positive group (p=0.035). The patients with MG (p=0.001) and WHO type B2 and B3 (p=0.007) have significantly higher PD-L2 scores. Multivariate logistic regression model showed the status of MG (OR 12.601, 95%CI 2.406-65.995, p=0.02) and age (OR 0.199, 95%CI 0.046-0.863, p=0.031) were significantly associated with the expression of PD-L2. The analysis of 33 patients with MG shows age was not associated with the expression of PD-L2 (OR 0.04, 95%CI 0.001-3.2, p=0.15). Conclusions A strong expression of PD-L2 in thymoma was significantly associated with thymomatous MG and WHO histologic type B2 and B3. In addition, PD-L2 may play a potential role in the pathogenesis of thymomatous MG.

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Immune biomarkers in thymic epithelial tumors: expression patterns, prognostic value and comparison of diagnostic tests for PD-L1

Cited by 32 publications

References 29 publications

Tumor Immunity is Related to 18F-FDG Uptake in Thymic Epithelial Tumor

Tumor Immunity is Related to 18F-FDG Uptake in Thymic Epithelial Tumor

Outcomes of surgical reconstruction of the superior vena cava syndrome in patients with locally advanced thymomas

The expression of Programmed death ligand 2 in patients with thymoma and thymomatous Myasthenia Gravis

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