Search

Introduction: Trophoblast cell surface antigen 2 (TROP2) is a transmembrane glycoprotein overexpressed in various cancer types. Although TROP2-targeting therapy is currently attracting attention, little is known about TROP2 expression in thymic carcinoma. Methods: TROP2 gene expression in thymic epithelial tumors was analyzed using RNA-sequencing (RNA-seq) data for 122 cases obtained from The Cancer Genome Atlas. Immunohistochemistry (IHC) staining with anti-TROP2 antibody (SP295) was performed in 26 cases of thymic carcinoma tissues surgically resected at Juntendo University. Results: RNA-seq data analysis from The Cancer Genome Atlas revealed that TACSTD2 (gene encoding TROP2) expression was significantly higher in thymic carcinoma than in thymoma (adjusted p = 6.64e-05). There was also a trend of increasing expression in the order of thymoma type B1, B2, B3, and thymic carcinoma. As for IHC in thymic carcinoma, TROP2 expression was localized to the membrane of cancer cells. Intensity 0, 1, and 2 was observed in six (23.1%), 11 (42.3%), and nine (34.6%) cases, respectively, leading to TROP2 positivity in 20 cases (76.9%). The median proportion of TROP2-positive tumor cells and the median H-score were 25.0% (range: 0%–100%) and 25.0 (range: 0–200), respectively. No relevant factors were identified in the analysis of TROP2 expression and patient background. Although not significant, high TROP2 expression (H-score ≥ 50) tended to be associated with shorter survival. Conclusions: TROP2 expression in thymic carcinoma was confirmed by both RNA-seq and IHC, with high expression observed in IHC for intensity (76.9%) and proportion. TROP2 could be a potential target in thymic carcinoma.

Introduction: Outcomes of immune checkpoint inhibitor (ICI) rechallenge in NSCLC remain uncertain. This study estimated the safety and efficacy of ICI rechallenge and compared rechallenge benefit among different reasons of initial ICI discontinuation in NSCLC. Methods: PubMed, EMBASE, and Cochrane Library were searched for studies on NSCLC retreated with ICI. Immune-related adverse events (irAEs), overall response rate (ORR), disease control rate (DCR), and progression-free survival (PFS) at initial ICI and rechallenge were analyzed. Results: A total of 15 studies including 442 patients between 2018 and 2022 were eligible for meta-analysis. The incidence of grade 3 or 4 irAE was lower in rechallenge than initial ICI (8.6% versus 17.8%, p < 0.001). Patients rechallenged with ICI had lower ORR and DCR than initial ICI (13.2% versus 42.4%, p < 0.001; 51.1% versus 74.0%, p < 0.001). The ORR and DCR to ICI rechallenge were both higher in patients who experienced disease progression after stopping ICI or irAE than patients with disease progression during ICI treatment (ORR: 46.2% versus 20% versus 11.4%, p = 0.003; DCR: 84.6% versus 90.0% versus 55.0%, p = 0.002). In addition, 34.7% of 69 patients with individual response to ICI and PFS experienced the same or better response to ICI rechallenge in comparison with initial ICI, although PFS in initial ICI was longer than that in ICI rechallenge (median: 8.90 versus 3.67 mo, hazard ratio = 0.44, 95% confidence interval: 0.33–0.59). Conclusions: ICI rechallenge had less severe toxicity than initial ICI treatment. Patients undergoing disease progression after ICI cessation or ICI discontinuation owing to irAE are more likely to benefit from ICI rechallenge in NSCLC.