Dendritic cells (DC) play a key role in the initiation of both antitumor immunity and immunological tolerance. It has been demonstrated that exposure to soluble factors produced by tumor cells modulates DC functions and induces tolerogenic DC differentiation. In this study, we investigated the effects of neuroblastoma cell line‐derived soluble factors on DC differentiation. Monocytes isolated from healthy volunteers were incubated with interleukin (IL)‐4 and granulocyte‐macrophage colony‐stimulating factor in the presence of culture supernatants from neuroblastoma cell lines. The culture supernatants from neuroblastoma cell lines, such as NLF and GOTO, partially blocked both downregulation of CD14 and upregulation of CD1a, and dramatically decreased IL‐12 and tumor necrosis factor (TNF)‐α production from mature DC, while no effect of SH‐SY5Y cell supernatant was noted. In addition, IL‐6 and IL‐10 production from monocytes was increased by the supernatants of NLF and GOTO cells at 24 hours after incubation. Furthermore, we evaluated DC functions through stimulation of invariant natural killer T (iNKT) cells. α‐Galactosylceramide‐pulsed DC co‐cultured with supernatants of NLF cells were unable to sufficiently stimulate iNKT cells. The decreased ability of iNKT cells to produce interferon (IFN)‐γ after stimulation with neuroblastoma cell line supernatant‐cultured DC was reversed by addition of IL‐12. CD40 expression and IL‐12 production in NLF‐sup‐treated DC were increased by addition of exogenous IFN‐γ. These results indicate that tolerogenic DC are induced in the neuroblastoma tumor microenvironment and attenuate the antitumor effects of iNKT cells. Interactions between iNKT cells and αGalCer‐pulsed DC have the potential to restore the immunosuppression of tolerogenic DC through IFN‐γ production.

It is essential to accurately and safely resect all tumors during surgery for multiple lung metastases. Here, we report a case of hepatoblastoma (HB) with multiple pulmonary nodules that ultimately underwent complete resection using combined three-dimensional image reconstruction and indocyanine green (ICG) fluorescence guidance. A 1-year-old boy was diagnosed with HB and multiple lung metastases. After intensive chemotherapy, complete resection with subsegmentectomy (S5 + 6) and partial resection (S3, S8) were performed. More than 100 pulmonary nodules, which remained visible on computed tomography (CT) despite additional postoperative chemotherapy, were subjected to pulmonary resection. We used the SYNAPSE VINCENT software (Fujifilm Medical, Tokyo, Japan) to obtain three-dimensional images of the nodules. We numbered each nodule, and 33 lesions of the right lung were resected by multiple wedge resections through a right thoracotomy, with the aid of palpation and ICG fluorescence guidance. One month after the right metastasectomy, resection of 64 lesions in the left lung was performed via left thoracotomy. Postoperative CT showed complete clearance of the lung lesions, and the patient remained disease-free for 15 months after the treatment. This case study confirms that the combination of three-dimensional localization and ICG fluorescence guidance allows for accurate and safe resection of nearly 100 lung metastases.

The role of immune checkpoint inhibitors in metastatic lung cancer has been established in recent years and the pretherapeutic profiles of the tumor microenvironment in responders have been increasingly reported. The role of salvage surgery and the immune profiles of the posttherapeutic specimens in patients achieving an objective response have rarely been studied. We report a case of metastatic lung cancer treated by anti‐programmed death‐1 Ab followed by surgical resection. The immune status of the tumor was assessed, showing germinal center formation, memory B cell infiltration, and a high frequency of interferon gamma ‐secreting T cells.

Purpose Hepatobiliary scintigraphy is a minimally invasive imaging method that evaluates bile flow dynamics. At our hospital, it has been performed for postoperative evaluation of patients with choledochal cysts (CC). This study evaluated the usefulness of biliary scintigraphy for predicting late complications in patients with CCs. Methods The study included pediatric patients with CC who underwent surgery at Chiba University Hospital from 1978 to 2020, followed by postoperative biliary scintigraphy and subsequent radiologic evaluation. The patients were divided into two groups according to the presence or absence of “biliary cholestasis” on biliary scintigraphy. Results The study included 108 patients, with a median age at surgery of 2 years and 11 months. The median follow-up period was 5203 days, with 11 hepatolithiasis cases and 8 cholangitis cases. No patients had cholangiocarcinoma. Twelve patients were considered to have “cholestasis” following biliary scintigraphy evaluation. There was no significant difference in the occurrence of hepatolithiasis between the cholestasis and non-cholestasis groups (p = 0.47), but cholangitis was significantly more common in the cholestasis group (p = 0.016). Conclusion Biliary cholestasis on postoperative hepatobiliary scintigraphy was a risk factor for cholangitis in patients with CCs. These particular patients should be monitored carefully.

PURPOSE Monocyte-derived dendritic cells (DCs) show limited or inhibited maturation in the tumor microenvironment. We previously reported that soluble factors released from neuroblastoma (NB) cells inhibit the differentiation of monocytes obtained from healthy adults into mature DCs. We herein investigated the inhibitory effect of NB-derived soluble factors on the maturation of monocytes obtained from children with malignant tumors towards DCs. METHODS Blood samples were collected from 25 children with untreated malignant solid tumors and 30 children with non-neoplastic diseases (control group). Purified monocytes were cultured with GM-CSF/IL-4 and matured into DCs. DCs were cultured with supernatants of NB cell lines and evaluated for maturation by FACS and IL-12 production. RESULTS Maturation toward DCs and IL-12 production were similarly observed in the malignant tumor group and the control group. DC maturation and IL-12 production were significantly suppressed in both groups when cultured with NB culture supernatant. CONCLUSION Monocytes obtained from children with malignant tumors were capable of maturing into DCs, which functioned similarly to those from control cases. NB-derived soluble factors inhibited the DC maturation and the function of DCs equally, regardless of the patient's tumor burden. Our results suggest the non-specific and universal immunoinhibitory effect of NB-derived soluble factors.