Recombinant human adenovirus type 5 promotes anti-tumor immunity via inducing pyroptosis in tumor endothelial cells.

Recombinant human type 5 adenovirus (H101) is an oncolytic virus used to treat nasopharyngeal carcinoma. Owing to the deletion of the E1B-55kD and E3 regions, H101 is believed to selectively inhibit nasopharyngeal carcinoma. Whether H101 inhibits other type of tumors via different mechanisms remains unclear. In this study we investigated the effects of H101 on melanomas. We established B16F10 melanoma xenograft mouse model, and treated the mice with H101 (1 × 108 TCID50) via intratumoral injection for five consecutive days. We found that H101 treatment significantly inhibited B16F10 melanoma growth in the mice. H101 treatment significantly increased the infiltration of CD8+ T cells and reduced the proportion of M2-type macrophages. We demonstrated that H101 exhibited low cytotoxicity against B16F10 cells, but the endothelial cells were more sensitive to H101 treatment. H101 induced endothelial cell pyroptosis in a caspase-1/GSDMD-dependent manner. Furthermore, we showed that the combination of H101 with the immune checkpoint inhibitor PD-L1 antibody (10 mg/kg, i.p., every three days for three times) exerted synergic suppression on B16F10 tumor growth in the mice. This study demonstrates that, in addition to oncolysis, H101 inhibits melanoma growth by promoting anti-tumor immunity and inducing pyroptosis of vascular endothelial cells.

An effective treatment and suspicious adverse reaction to Ibrutinib in a patient diagnosed with splenic B-cell lymphoma/leukaemia with prominent nucleoli: A first case report.

RATIONALE: Splenic B-cell lymphoma/leukemia with prominent nucleoli (SBLPN) is a new classification, which is so rare that it lacks clinical data. PATIENT CONCERNS: An increased proportion of prolymphocytes (84%) in the bone marrow smear. Whole exon sequence analysis revealed a TP53 mutation. DIAGNOSES: Combining the clinical features with laboratory test results led to a diagnosis of SBLPN which was made according to the 5th edition of the WHO classification of hematolymphoid tumors, although the patient was diagnosed with B-PLL when guided by the 4th edition of the WHO classification. INTERVENTIONS: The use of Ibrutinib as an effective treatment. OUTCOMES: The patient was in complete remission after 5 months of Ibrutinib and then died of sudden aortic dissection. LESSONS: Ibrutinib was an effective regimen for SBLPN. Aortic dissection might be considered as a suspicious adverse reaction to Ibrutinib.