Abstract
BackgroundThe significance of epithelial‐mesenchymal transition (EMT) and immune checkpoint proteins in thymic carcinoma remains unknown. We examined the clinical significance of EMT, tumor‐infiltrating lymphocytes expressing the immune checkpoint protein, programmed cell death 1 (PD‐1 + TILs), and the expression of PD‐1 ligand 1 (PD‐L1) in thymic carcinoma (TC). We also investigated the relationships between these immune checkpoint proteins and the EMT status and examined the impact of induction chemotherapy on patients with tumors that express these proteins.MethodsThe relationship between PD‐1 + TILs/PD‐L1 and clinicopathological findings including EMT was investigated by immunohistochemistry (IHC) of surgically resected samples from 43 patients with TC. In 15 patients receiving induction therapy (IT), those factors were compared before and after IT.ResultsWith IHC, 26 cases (60.5%) were positive for PD‐L1, and 19 cases were positive for PD‐1 + TILs (44.2%). The disease‐free survival rate in patients showing EMT and who were PD‐1/PD‐L1 positive was significantly worse compared to negative cases (EMT; P = 0.0095, PD‐1; P = 0.001, PD‐L1; P = 0.0037). We found a significant relationship between PD‐L1 and EMT status (P = 0.01). In patients who received IT, PD‐L1 increased, and the change was strongly correlated with EMT status (P = 0.01).ConclusionEpithelial‐mesenchymal transition, PD‐L1, and PD‐1 + TILs have prognostic impact, and PD‐L1 is correlated with EMT status. PD‐L1 expression after IT was significantly higher compared to before IT and was correlated with the EMT change. Thus, PD‐L1 may be upregulated during EMT, and anti‐PD‐1/PD‐L1 immunotherapy may provide reliable treatment of TC in combination with chemotherapy.
Highlights
Thymic carcinoma (TC) is an aggressive thoracic malignancy
3.4 | Upregulation of programmed cell death 1 (PD‐1) ligand 1 (PD‐L1) The correlation between PD‐L1 IHC status (TPS) and alteration in epithelial‐mesenchymal transition (EMT) markers after induction therapy (IT). To explore whether these relationships between PD‐L1 expression and EMT status after IT in thymic carcinoma (TC) are similar to our previous report of non‐small cell lung cancer (NSCLC),[12] we performed IHC staining of those molecules in 15 comparable cases who underwent IT followed by surgery (Figure 4A)
We analyzed IHC staining of EMT markers and the immune checkpoint proteins, PD‐1 and PD‐L1, in clinical samples of TC obtained by surgical resection
Summary
Thymic carcinoma (TC) is an aggressive thoracic malignancy. Because of the small number of cases, the biological and oncological characteristics of TC are poorly understood, and no standard treatment strategy has been established. Using immunohistochemistry (IHC) analysis of surgically resected NSCLC samples before and after IT, we showed that PD‐L1 expression is correlated with EMT status.[12]. | 217 immune checkpoint proteins (PD‐1/PD‐L1) and the clinical background including EMT markers using IHC staining of TC clinical samples obtained by surgical resection. 2.2 | IHC staining analysis of EMT markers and PD‐1/PD‐L1 expression in clinical samples. Using clinical samples obtained from enrolled patients with TC, we performed IHC with several antibodies that recognize cancer‐associated proteins, including c‐kit (TC marker), PD‐1/PD‐L1 (immune checkpoint proteins), and E‐cad, N‐ cad, and TGF‐β (EMT‐associated proteins). PD‐L1 expression was evaluated as the percentage of cells staining positive for PD‐L1 (tumor proportion score, TPS), and PD‐L1 positive was defined as TPS ≥50%. P values
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