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Introduction Although immune checkpoint inhibitors offer significant therapeutic benefits to patients with advanced cancer, they can also cause a variety of immune‐related adverse events. As immune checkpoint inhibitors are being widely used, rare immune‐related adverse events are being reported. Case presentation A 70‐year‐old man with advanced salivary duct carcinoma was treated with pembrolizumab following radiotherapy. After receiving two doses of pembrolizumab, the patient experienced symptoms such as micturition pain and hematuria. Immune‐related cystitis was suspected, and the patient underwent a bladder biopsy and bladder hydrodistension. Histological analysis revealed non‐neoplastic bladder mucosa with CD8‐positive lymphocyte‐dominant inflammatory cell infiltration, consistent with immune‐related cystitis. The patient's bladder symptoms improved postoperatively without steroid administration. Conclusion Although steroids are commonly administered to treat immune‐related adverse events, bladder hydrodistension may be a promising treatment option for immune‐related cystitis to avoid administration of steroids, which may impair the therapeutic effect of immune checkpoint inhibitors.

Advanced bladder cancer (BC) (local invasive and/or metastatic) is not curable even with cytotoxic chemotherapy, immune checkpoint inhibitors, and targeted treatment. Targeting GSK-3β is a promising novel approach in advanced BC. The induction of autophagy is a mechanism of secondary resistance to various anticancer treatments. Our objectives are to investigate the synergistic effects of GSK-3β in combination with autophagy inhibitors to evade GSK-3β drug resistance. Small molecule GSK-3β inhibitors and GSK-3β knockdown using siRNA promote the expression of autophagy-related proteins. We further investigated that GSK-3β inhibition induced the nucleus translocation of transcription factor EB (TFEB). Compared to the GSK-3β inhibition alone, its combination with chloroquine (an autophagy inhibitor) significantly reduced BC cell growth. These results suggest that targeting autophagy potentiates GSK-3β inhibition-induced apoptosis and retarded proliferation in BC cells.

Abstract Background Sarcomatoid carcinoma is a rare, high-grade malignancy with epithelial and mesenchymal components. It may be a good candidate for immunotherapy because it is associated with overexpression of programmed cell death ligand 1. Sarcomatoid urothelial carcinoma (UC) of the upper urinary tract is extremely rare. Here we report the first case of sarcomatoid UC of the renal pelvis that responded to immunotherapy. Case presentation A 79-year-old man was referred to our hospital complaining of various symptoms, including anorexia and abdominal pain. A computed tomography scan revealed a right atrial tumor, a 9 cm left renal mass with a renal vein tumor thrombus, para-aortic lymphadenopathy, and multiple small lung nodules. The patient underwent resection of the right atrial tumor. Pathological analysis of the tumor did not lead to an accurate diagnosis even after several rounds of immunohistochemistry. He underwent a needle biopsy of the left kidney and was initially diagnosed with collecting duct carcinoma, a rare subtype of renal cell carcinoma (RCC). Following the initial diagnosis, immunotherapy with nivolumab and ipilimumab commenced. Thereafter, almost all lesions, including the left renal tumor, were reduced in size. However, he underwent a left nephrectomy approximately a year after beginning immunotherapy due to repeated left renal bleeding. Histological examination of the nephrectomy specimen revealed two forms of cancer—sarcomatoid UC and conventional high-grade UC. Two months after surgery, the patient was found to have new lung metastases. He underwent chemotherapy with gemcitabine and cisplatin, followed by immunotherapy with pembrolizumab. However, both treatments were ineffective. The patient died of cancer 19 months after his first admission. Conclusions The presented case of sarcomatoid UC of the renal pelvis that partially responded to immunotherapy suggests that immunotherapy can be a promising treatment for sarcomatoid UC.

Abstract Immune checkpoint inhibitors (ICI) have dramatically changed the treatment of metastatic renal cell carcinoma (mRCC). Although many studies have reported biomarkers as predicting the efficacy of ICI in mRCC, they remain controversial and have challenges to apply in real-world practice. We evaluated prognostic significance of multiple molecules associated with tumor immunity in patients treated with ICI. The molecules were detected in tumor tissues by immunohistochemical staining. We identified CD8-positive T cells and CD68-positive macrophages infiltrating into the tumor tissue as significant favorable prognostic factors for ICI treatment. Conversely, high expression of CD4-positive T cells was associated with poor response to ICI. Furthermore, we demonstrated that scoring for the expression status of these three molecules provides a remarkably accurate biomarker in patients with mRCC. Even the classical approach of immunohistochemistry could predict the outcome of ICI treatment by assessing the combined status of tumor-infiltrating immune cells.

Introduction Tumors in the fibroma–thecoma group are benign tumors, typically found in the ovaries of postmenopausal women and occasionally develop in the testes. These tumors are mostly treated with radical orchiectomy because preoperative diagnosis confirming the benign nature is difficult. Case presentation A 40‐year‐old man was incidentally pointed out to have a right intrascrotal mass, measuring approximately 10 cm on computed tomography. Malignant testicular tumor was suspected based on the location and size of the tumor. The patient underwent right radical orchiectomy. Histologically, the tumor had no evidence of malignancy, and the diagnosis of tumors in the fibroma–thecoma group was made. The patient had no recurrence 8 months after surgery. Conclusion Intrascrotal tumors in the fibroma–thecoma group are rare benign tumors and mostly treated with radical orchiectomy due to concerns about malignancies. Further investigation is needed for accurate preoperative diagnosis, and we should be aware of these rare tumors.

Abstract Glycogen synthase kinase-3 beta (GSK-3β), a serine/threonine kinase, has been identified as a potential therapeutic target in human bladder cancer. In the present study, we investigated the antitumor effect of a small molecule GSK-3β inhibitor, 9-ING-41, currently in clinical studies in patients with advanced cancer, in bladder cancer cell lines. We found that treatment with 9-ING-41 leads to cell cycle arrest, autophagy and apoptosis in bladder cancer cells. The autophagy inhibitor chloroquine potentiated the antitumor effects of 9-ING-41 when tested in combination studies. Our findings also demonstrate that 9-ING-41 enhanced the growth inhibitory effects of gemcitabine or cisplatin when used in combination in bladder cancer cells. Finally, we found that 9-ING-41 sensitized bladder cancer cells to the cytotoxic effects of human immune effector cells. Our results provide a rationale for the inclusion of patients with advanced bladder cancer in clinical studies of 9-ING-41.