Exosomes are small membrane vesicles that are secreted by a multitude of cell types. The exosomes derived from dendritic cells (Dex), tumor cells (Tex), and malignant effusions demonstrate immunomodulatory functions, and are even under clinical trial for cancer treatments. In this study we report the phase I clinical trial of the ascites-derived exosomes (Aex) in combination with the granulocyte-macrophage colony-stimulating factor (GM-CSF) in the immunotherapy of colorectal cancer (CRC). The Aex isolated by sucrose/D(2)O density gradient ultracentrifugation are 60-90-nm vesicles that contain the diverse immunomodulatory markers of exosomes and tumor-associated carcinoembryonic antigen (CEA). Totally 40 patients (HLA-A0201(+)CEA(+)) with advanced CRC were enrolled in the study, and randomly assigned to treatments with Aex alone or Aex plus GM-CSF. Patients in both groups received a total of four subcutaneous immunizations at weekly intervals. We found that both therapies were safe and well tolerated, and that Aex plus GM-CSF but not Aex alone can induce beneficial tumor-specific antitumor cytotoxic T lymphocyte (CTL) response. Therefore, our study suggests that the immunotherapy of CRC with Aex in combination with GM-CSF is feasible and safe, and thus can serve as an alternative choice in the immunotherapy of advanced CRC.

PURPOSE As yet, no checkpoint inhibitor has been approved to treat nasopharyngeal carcinoma (NPC). This study was aimed to evaluate the antitumor activity, safety, and biomarkers of toripalimab, a new programmed death-1 (PD-1) inhibitor for recurrent or metastatic NPC (RM-NPC) refractory to standard chemotherapy. PATIENTS AND METHODS In this single-arm, multicenter phase II study, patients with RM-NPC received 3 mg/kg toripalimab once every 2 weeks via intravenous infusion until confirmed disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR). The secondary end points included safety, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). RESULTS Among all 190 patients, the ORR was 20.5% with median DOR 12.8 months, median PFS 1.9 months, and median OS 17.4 months. Among 92 patients who failed at least two lines of systemic chemotherapy, the ORR was 23.9%. The ORRs were 27.1% and 19.4% in PD-L1+ and PD-L1− patients, respectively ( P = .31). Patients with ≥ 50% decrease of plasma Epstein-Barr virus (EBV) DNA copy number on day 28 had significantly better ORR than those with <50% decrease, 48.3% versus 5.7% ( P = .0001). Tumor mutational burden had a median value of 0.95 muts/mega-base in the cohort and had no predictive value for response. Whole-exome sequencing results from 174 patients revealed that the patients with genomic amplification in 11q13 region or ETV6 genomic alterations had poor responses to toripalimab. CONCLUSION The POLARIS-02 study demonstrated a manageable safety profile and durable clinical response of toripalimab in patients with chemorefractory metastatic NPC. An early decrease in plasma EBV DNA copy number correlated with favorable response.

Circulating RNAs in serum, plasma or other body liquid have emerged as useful and highly promising biomarkers for noninvasive diagnostic application. Herein, we aimed to establish a serum long non-coding RNAs (lncRNAs) signature for diagnosing nasopharyngeal carcinoma (NPC). In this study, we recruited a cohort of 101 NPC patients, 20 patients with chronic nasopharyngitis (CN), 20 EBV carriers (EC) and 101 healthy controls. qRT-PCR was performed with NPC cells and serum samples to screen a pool of 38 NPC-related lncRNAs obtained from the LncRNADisease database. A profile of three circulating lncRNAs (MALAT1, AFAP1-AS1 and AL359062) was established for NPC diagnosis. By Receiver Operating Characteristic (ROC) curve analysis, this three-lncRNA signature showed high accuracy in discriminating NPC from healthy controls (AUC = 0.918), CN (AUC = 0.893) or EC (AUC = 0.877). Furthermore, high levels of these three lncRNAs were closely related to advanced NPC tumor node metastasis stages and EBV infection. Serum levels of these three lncRNAs declined significantly in patients after therapy. Our present study indicates that circulating MALAT1, AFAP1-AS1 and AL359062 may represent novel serum biomarkers for NPC diagnosis and prognostic prediction after treatment.

Lung cancer stem cells are a subpopulation of cells critical for lung cancer progression, metastasis, and drug resistance. Thioridazine, a classical neurological drug, has been reported with anticancer ability. However, whether thioridazine could inhibit lung cancer stem cells has never been studied. In our current work, we used different dosage of thioridazine to test its effect on lung cancer stem cells sphere formation. The response of lung cancer stem cells to chemotherapy drug with thioridazine treatment was measured. The cell cycle distribution of lung cancer stem cells after thioridazine treatment was detected. The in vivo inhibitory effect of thioridazine was also measured. We found that thioridazine could dramatically inhibit sphere formation of lung cancer stem cells. It sensitized the LCSCs to chemotherapeutic drugs 5-FU and cisplatin. Thioridazine altered the cell cycle distribution of LCSCs and decreased the proportion of G0 phase cells in lung cancer stem cells. Thioridazine inhibited lung cancer stem cells initiated tumors growth in vivo. This study showed that thioridazine could inhibit lung cancer stem cells in vitro and in vivo. It provides a potential drug for lung cancer therapy through targeting lung cancer stem cells.