Anti-programmed cell death-1 (PD-1) antibodies has been approved to treat HCC. Some PD-1 ligands (PD–L1 and PD–L2) negative tumors respond to treatment of anti-PD-1 antibodies, and this fact may be caused by the expression of PD-1 ligands on non-tumor cells. PD–L1 was recently found to be expressed on CD14+ cells from cancer patients. We investigate PD-1 ligands expression on CD14+ cells of patients with HCC and the role of CD14+ cells in an antitumor response. In this study, 87 patients diagnosed with HCC were enrolled. CD14+ cells from patients with HCC expressed PD–L1 (4.5–95.5%) and PD–L2 (0.2–95.0%). According to cut-off values, we classified patients as those either with PD–L1+PD–L2+CD14+ cells or other types of CD14+ cells. The overall survival of patients with PD–L1+PD–L2+CD14+ cells was shorter than that of patients with other types of CD14+ cells (p = 0.0023). PD–L1+PD–L2+CD14+ cells produced IL-10 and CCL1, and showed little tumoricidal activity against HepG2 cells. The tumoricidal activity of CD8+ cells from patients with PD–L1+PD–L2+CD14+ cells were suppressed by co-cultivation with CD14+ cells from the syngeneic patient. Furthermore, anti-PD-1 antibody restored their tumoricidal activity of CD8+ cells. In conclusion, some patients with HCC have PD–L1+PD–L2+CD14+ cells that suppress their antitumor response. These inhibitory functions of CD14+ cells may be associated with a poor prognosis in these patients.

immune-related adverse events (irAes) are induced by immune checkpoint inhibitors (icis). Liver is one of the main target organs which irAEs occur and we investigated the influence of liver dysfunction on prognosis of patients after ICIs. From July 2014 to December 2018, 188 patients with diverse cancers who received icis (nivolumab or pembrolizumab) were enrolled. twenty-nine patients experienced liver dysfunction of any grades after ICIs. Progression-free survival (PFS) was significantly shorter in the liver dysfunction-positive group than in the liver dysfunction-negative group, and a similar result was obtained for overall survival (oS). Multiple logistic regression analysis revealed liver metastasis and alanine aminotransferase before icis were associated with a higher incidence of liver dysfunction after ICIs. Regardless of liver metastasis, PFS and OS were significantly shorter in the liver dysfunction-positive group. in conclusion, this study suggests liver dysfunction is associated with poor prognosis in patients after icis with diverse cancers. Cancer was the second most common cause of death in the last decade, and was responsible for an estimated 9.6 million deaths worldwide in 2018 1. Cancer is treated by surgical resection, radiation and chemotherapy, but the mortality rate in cancer patients is still high. Therefore, new strategies to treat cancer are needed. Recently, immunotherapy has become a mainstay of treatment of cancer. Antibodies against cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) and its ligands (PD-L1/PD-L2) can modulate the immune response to cancer clearance in a various human malignancies. The PD-1 pathway operates in the tumor microenvironment, unlike CTLA-4, which mainly works in the lymph nodes 2. PD-1 interacts with its ligands on the surface of tumor cells and tumor-associated macrophages, dendritic cells, fibroblasts, and activated T cells in the immune milieu 3-6. The binding of PD-1 with its ligands block antitumor activity of T cell 7-9. Nivolumab and pembrolizumab are fully humanized immunoglobulin G4 PD-1 immune checkpoint inhibitor (ICI) antibodies that selectively block the interaction of the PD-1 receptor and its ligands 10,11. These inhibitors have significant clinical activity and have improved prognosis in multiple cancer types, including non-small-cell lung cancer, renal cell carcinoma, urothelial carcinoma, gastric cancer, head and neck squamous cell carcinoma, malignant melanoma, and hepatocellular carcinoma 11-21. Blocking immunosuppressive ligand receptor interactions enhances the anticancer effects of lymphocytes. However, these molecules are also involved in healthy immune tolerance, and therefore adverse reactions to selfantigens can occur. The adverse events caused by autoimmune reactions are currently denoted as immune-related adverse events (irAEs) to differentiate them from idiosyncratic drug-induced organ damage 22. Most patients with irAEs can be managed, but some patients treated with ICIs have died because of ir...

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Background Although the 2018 revised International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification was proposed recently, until now, no reports have been made comparing the association of renal prognosis between the 2018 revised ISN/RPS classification and the 2003 ISN/RPS classification. The present study aimed to assess the usefulness, especially of activity and chronicity assessment, of the 2018 revised ISN/RPS classification for lupus nephritis (LN) in terms of renal prognosis compared to the classification in 2003. Methods We retrospectively collected medical records of 170 LN patients from the database of renal biopsy at Fujita Health University from January 2003 to April 2019. Each renal biopsy specimen was reevaluated according to both the 2003 ISN/RPS classification and the 2018 revised ISN/RPS classification. Renal endpoint was defined as a 30% decline of estimated glomerular filtration rate (eGFR). Results A total of 129 patients were class III/IV±V (class III, 44 patients; class IV, 35 patients; class III/IV+V, 50 patients). The mean age was 42 years, 88% were female, and the median observation period was 50.5 months. Renal prognosis was significantly different among the classes and significantly poor in the patients with higher modified National Institute of Health (mNIH) chronicity index (C index, ≥ 4) by a log-rank test (p = 0.05 and p = 0.02, respectively). By Cox proportional hazard models, only the C index was significantly associated with renal outcome (hazard ratio 1.32, 95% CI 1.11–1.56, p ≤ 0.01), while the classes, the 2003 activity and chronicity subdivision, and the mNIH activity index had no significant association with renal outcome. Each component of the C index was significantly associated with renal outcome in different models. Conclusion This study demonstrates that the 2018 revised ISN/RPS classification was more useful in terms of association with renal prognosis compared to the 2003 ISN/RPS classification.

The natural history of intracholecystic papillary neoplasm (ICPN), especially the speed of growth from small benign to a carcinomatous lesion, is quite unrevealed. Here, we report an extremely rare case of ICPN, in which the papillary lesion was observed transforming from small and benign to malignant using abdominal ultrasound (AUS) over 2 years during routine health checks. A 44-year-old man underwent a routine health check-up. The initial AUS showed a small sessile polyp in the gallbladder, which enlarged slightly at the next AUS, a year later. In the third year, the polypoid lesion enlarged markedly, with a maximum diameter of 10 × 9 × 7 mm. Therefore, a laparoscopic cholecystectomy was performed. Microscopically, the 10 mm tumor had intracytoplasmic mucus, and a clear cytoplasm compatible with gastric-type features. Immunohistochemical analysis showed positive staining of atypical cells for MUC6 and PAS. These findings led to the diagnosis of ICPN with high-grade intraepithelial neoplasia of the gastric type. In conclusion, sessile polyps with rapid growth might be a crucial finding in the early stage of ICPN.