Papers

• GRIK2 is a target for bladder cancer stem-like cell-targeting immunotherapy.
  Haruka Miyata, Yoshihiko Hirohashi, Shuhei Yamada, Junko Yanagawa, Aiko Murai, Shinichi Hashimoto, Serina Tokita, Kanta Hori, Takashige Abe, Terufumi Kubo, Tomohide Tsukahara, Takayuki Kanaseki, Nobuo Shinohara, Toshihiko Torigoe
  Cancer immunology, immunotherapy : CII, 71, 4, 795, 806, Apr. 2022, [International Magazine]
  English, Scientific journal, Recent studies have revealed that treatment-resistant cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) can be targeted by cytotoxic T lymphocytes (CTLs). CTLs recognize antigenic peptides derived from tumor-associated antigens; thus, the identification of tumor-associated antigens expressed by CSCs/CICs is essential. Human leucocyte antigen (HLA) ligandome analysis using mass spectrometry enables the analysis of naturally expressed antigenic peptides; however, HLA ligandome analysis requires a large number of cells and is challenging for CSCs/CICs. In this study, we established a novel bladder CSC/CIC model from a bladder cancer cell line (UM-UC-3 cells) using an ALDEFLUOR assay. CSCs/CICs were isolated as aldehyde dehydrogenase (ALDH)-high cells and several ALDHhigh clone cells were established. ALDHhigh clone cells were enriched with CSCs/CICs by sphere formation and tumorigenicity in immunodeficient mice. HLA ligandome analysis and cap analysis of gene expression using ALDHhigh clone cells revealed a distinctive antigenic peptide repertoire in bladder CSCs/CICs, and we found that a glutamate receptor, ionotropic, kainite 2 (GRIK2)-derived antigenic peptide (LMYDAVHVV) was specifically expressed by CSCs/CICs. A GRIK2 peptide-specific CTL clone recognized GRIK2-overexpressing UM-UC-3 cells and ALDHhigh clone cells, indicating that GRIK2 peptide can be a novel target for bladder CSC/CIC-targeting immunotherapy.
• Abscopal effect following nivolumab induction in a patient with metastatic renal cell carcinoma-unique pathological features of the primary specimen: A case report.
  Kanta Hori, Yoshihiko Hirohashi, Toshiki Aoyagi, Narumi Taniguchi, Masashi Murakumo, Haruka Miyata, Toshihiko Torigoe, Takashige Abe, Nobuo Shinohara, Ken Morita
  Experimental and therapeutic medicine, 19, 3, 1903, 1907, Mar. 2020, [International Magazine]
  English, Scientific journal, The case of a patient with metastatic renal cell carcinoma who exhibited the abscopal effect following treatment by anti-programmed death-1 (PD-1) antibody is presented. A 40-year-old woman was diagnosed with an 8.2-cm renal tumor without distant metastases, and radical nephrectomy was subsequently performed. Pathological examination revealed a clear cell renal cell carcinoma. At 3 months after surgery, the patient developed one lung metastasis. Following treatment with interferon and three types of tyrosine kinase inhibitors, anti-PD1 antibody (nivolumab) was started. During the treatment, para-aortic/supraclavicular lymph nodes and several lung lesions remained, although other lesions decreased markedly. The patient was subsequently treated by palliative radiotherapy to the para-aortic and supraclavicular lymph nodes for pain control. After the radiotherapy, the lung lesions previously refractory to nivolumab started to decrease, probably due to an abscopal effect. Additionally, the laboratory data and Karnofsky Performance Status improved. Histological re-examination of the primary lesion revealed heterogeneity of the immunological microenvironment, which may be associated with the heterogeneity of treatment sensitivity.