3 results on '"Kei Miyoshi"'
Search Results
2. PTPN3 is a potential target for a new cancer immunotherapy that has a dual effect of T cell activation and direct cancer inhibition in lung neuroendocrine tumor
- Author
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Satoko Koga, Hideya Onishi, Shogo Masuda, Akiko Fujimura, Shu Ichimiya, Kazunori Nakayama, Akira Imaizumi, Kenichi Nishiyama, Masayuki Kojima, Kei Miyoshi, Katsuya Nakamura, Masayo Umebayashi, Takashi Morisaki, and Masafumi Nakamura
- Subjects
PTPN3 ,Lung net ,Cancer immunotherapy strategy ,Cancer suppression ,Lymphocyte activation ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
In our previous study, we found that inhibition of protein tyrosine phosphatase non-receptor type 3 (PTPN3), which is expressed in lymphocytes, enhances lymphocyte activation, suggesting PTPN3 may act as an immune checkpoint molecule. However, PTPN3 is also expressed in various cancers, and the biological significance of PTPN3 in cancer cells is still not well understood, especially for lung neuroendocrine tumor (NET).Therefore, we analyzed the biological significance of PTPN3 in small cell lung cancer and examined the potential for PTPN3 inhibitory treatment as a cancer treatment approach in lung NET including small cell lung cancer (SCLC) and large cell neuroendocrine cancer (LCNEC).Experiments in a mouse xenograft model using allo lymphocytes showed that PTPN3 inhibition in SCLC cells enhanced the anti-tumor effect of PTPN3-suppressed activated lymphocytes. In addition, PTPN3 was associated with increased vascularization, decreased CD8/FOXP3 ratio and cellular immunosuppression in SCLC clinical specimens. Experiments in a mouse xenograft model using autocrine lymphocytes also showed that PTPN3 inhibition in LCNEC cells augmented the anti-tumor effect of PTPN3-suppressed activated lymphocytes. In vitro experiments showed that PTPN3 is involved in the induction of malignant traits such as proliferation, invasion and migration. Signaling from PTPN3 is mediated by MAPK and PI3K signals via tyrosine kinase phosphorylation through CACNA1G calcium channel. Our results show that PTPN3 suppression is associated with lymphocyte activation and cancer suppression in lung NET. These results suggest that PTPN3 suppression could be a new method of cancer treatment and a major step in the development of new cancer immunotherapies.
- Published
- 2021
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3. PTPN3 is a potential target for a new cancer immunotherapy that has a dual effect of T cell activation and direct cancer inhibition in lung neuroendocrine tumor
- Author
-
Kazunori Nakayama, Masafumi Nakamura, Masayuki Kojima, Katsuya Nakamura, Kei Miyoshi, Shu Ichimiya, Hideya Onishi, Kenichi Nishiyama, Shogo Masuda, Akira Imaizumi, Satoko Koga, Akiko Fujimura, Masayo Umebayashi, and Takashi Morisaki
- Subjects
0301 basic medicine ,Cancer Research ,medicine.medical_treatment ,T cell ,PTPN3, protein tyrosine phosphatase non-receptor type3 ,03 medical and health sciences ,0302 clinical medicine ,Cancer immunotherapy ,ERK, extracellular signal-regulated kinase ,EMT, Epithelial-mesenchymal transition ,medicine ,EGFR, Epidermal growth factor receptor ,ZAP70, zeta-chain-associated protein kinase 70 ,VEGFA, Vascular endothelial growth factor A ,Autocrine signalling ,Lung net ,Cancer immunotherapy strategy ,Lymphocyte activation ,RC254-282 ,Original Research ,CACNA1G, Calcium Voltage-Gated Channel Subunit Alpha1 G ,Large-cell neuroendocrine cancer ,Chemistry ,Cancer ,FOXP3 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,CDDP, Cis-diamminedichloro-platinum ,medicine.disease ,AKT, protein kinase b ,LCK, lymphocyte-specific protein tyrosine kinase ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,GAPDH, glyceraldehyde-3-phosphate dehydrogenase ,PTPN3 ,030220 oncology & carcinogenesis ,Cancer cell ,Cancer research ,Cancer suppression ,Tyrosine kinase ,PTP, protein tyrosine phosphatase - Abstract
Highlights • PTPN3 suppression associates with lymphocyte activation and cancer suppression. • PTPN3 is involved in the induction of malignant traits. • PTPN3 is associated with cellular immunosuppression. • Signals from PTPN3 go through MAPK and PI3K signaling. • PTPN3-inhibited lung NET cells enhance PTPN3-suppressed activated lymphocytes., In our previous study, we found that inhibition of protein tyrosine phosphatase non-receptor type 3 (PTPN3), which is expressed in lymphocytes, enhances lymphocyte activation, suggesting PTPN3 may act as an immune checkpoint molecule. However, PTPN3 is also expressed in various cancers, and the biological significance of PTPN3 in cancer cells is still not well understood, especially for lung neuroendocrine tumor (NET).Therefore, we analyzed the biological significance of PTPN3 in small cell lung cancer and examined the potential for PTPN3 inhibitory treatment as a cancer treatment approach in lung NET including small cell lung cancer (SCLC) and large cell neuroendocrine cancer (LCNEC). Experiments in a mouse xenograft model using allo lymphocytes showed that PTPN3 inhibition in SCLC cells enhanced the anti-tumor effect of PTPN3-suppressed activated lymphocytes. In addition, PTPN3 was associated with increased vascularization, decreased CD8/FOXP3 ratio and cellular immunosuppression in SCLC clinical specimens. Experiments in a mouse xenograft model using autocrine lymphocytes also showed that PTPN3 inhibition in LCNEC cells augmented the anti-tumor effect of PTPN3-suppressed activated lymphocytes. In vitro experiments showed that PTPN3 is involved in the induction of malignant traits such as proliferation, invasion and migration. Signaling from PTPN3 is mediated by MAPK and PI3K signals via tyrosine kinase phosphorylation through CACNA1G calcium channel. Our results show that PTPN3 suppression is associated with lymphocyte activation and cancer suppression in lung NET. These results suggest that PTPN3 suppression could be a new method of cancer treatment and a major step in the development of new cancer immunotherapies.
- Published
- 2021
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