e14041 Background: Anti-PD-1 antibodies (nivolumab) are effective in the treatment of many cancers. There is a demand for less invasive biomarkers. Peripheral and tumor CD8+PD-1+ T cells share neoantigen-specific T-cell receptors (TCRs), and are presumed to act as effector T cells with an antitumor effect at the tumor site. We analyzed the diversity in terms of TCR α and β repertoires on peripheral CD8+PD-1+ T cells, tumor mutation burden and examined the relationship between this diversity and therapeutic effect of nivolumab. Methods: This study used patients administered nivolumab after exhibiting no response to chemotherapy for recurrence following surgery. Peripheral blood mononuclear cells were collected from patients before administration of nivolumab. CD8+PD-1+ T cells were subjected to FACS sorting, NGS-based TCR repertoire analysis was performed by Repertoire Genesis Inc., and TCR diversity was evaluated statistically. This study was approved by the Ethical Committee of Hyogo College of Medicine. Results: Six of 12 patients responded to treatment. Upon comparing these responders (CR, PR) with non-responders (SD, PD), there were no differences in the proportion of PD-1+ in CD8+ T cells and the proportion of CD8+PD-1+ T cells in gated lymphocytes. TCR α diversity was significantly higher among responders than non-responders based on Shannon index, Simpson index and DE50 (P < 0.05, P < 0.05, P < 0.01, respectively). TCR β diversity was also significantly higher among responders than non-responders based on Shannon index, Simpson index and DE50 (all P < 0.01). Progression-free survival (PFS) was 371 days for responders and 148 days for non-responders. Overall survival (OS) was 633 days for responders and 308 days for non-responders, showing a significant difference between the groups. TCR repertoire was proportional to TMB. Clones found in multiple patients were more frequent in indel than in SNP. Conclusions: TCR repertoire analysis was performed on CD8+PD-1+ T cells in easily-obtainable peripheral blood before nivolumab treatment in patients with NSCLC, and nivolumab was observed to be effective in patients with high TCR diversity. This result indicates the TCR diversity of peripheral CD8+PD-1+ T cells is effective as a predictive biomarker for response to ICI therapy.
A 70-year-old man diagnosed with right-sided malignant epithelial pleural mesothelioma, underwent pleurectomy/decortication after three courses of neoadjuvant chemotherapy. He had a history of mitral valve replacement and maze procedure with median sternotomy, and the procedures resulted in strong adhesion from the apex to the mediastinal side. In particular, the peeling of the area where the tumor invaded the pericardium required the most attention; however, the involved pericardium could be partially resected without damaging the right atrium. Finally, en bloc macroscopic complete resection with the entire pleura was successfully performed without conversion to extrapleural pneumonectomy.
e18542 Background: Cisplatin plus pemtrexte is first line chemotherapy for Malignant Pleural Mesothelioma (MPM). In multimodality include extrapleural pneumonectomy (EPP), chemotherapy is essential. Excision repair cross-complementing group 1 gene (ERCC1) is important for platinum-induced DNA adduct repair. We evaluate the association of overall survival (OS) and the expression of TS, ERCC1 in MPM multimodality therapy. Methods: Forty six MPM patients underwent multimodality includes Extrapleural Pneumonectomy (EPP) at Hyogo College of Medical, Nishinomiya, Japan from April 2004 to October 2013. All patients received neoadujvant chemotherapy (Cisplatin/Pemetrexed) followed by EPP. Paraffin embedded surgical sample was used for immunohistochemistry to evaluate the expression of TS, ERCC1. Overall survival (OS) from the time of surgery was determined by Kaplan-Meier method and results compared by log-rank test. Results: The median OS of 46 MPM patients was 24.5 months (95% confidence interval [CI], 0.0082-47.2 months). The high ERCC1 expression related better survival than the low ERCC1 expression (43.6 vs.15.2 months, P=0.023). There was no correlation between TS expression and OS (39.2 vs. 22.0 months for low and high levels, respectively; P=0.80).Twenty six patients received postoperative hemithorax radiation. In subgroup analysis of patients who did not receive hemisothax radiation, ERCC1 positive was better than ERCC1 negative (15.4 months vs. 10.0 months, P=0.089). Conclusions: The high expression of ERCC1 was associated with prolonged survival in neoadujvant chemotherapy (Cisplatin/Pemetrexed) followed by EPP. It appears that the expression of ERCC1 had prognostic value.
