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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

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 biol...

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Autores principales: Koga, Satoko, Onishi, Hideya, Masuda, Shogo, Fujimura, Akiko, Ichimiya, Shu, Nakayama, Kazunori, Imaizumi, Akira, Nishiyama, Kenichi, Kojima, Masayuki, Miyoshi, Kei, Nakamura, Katsuya, Umebayashi, Masayo, Morisaki, Takashi, Nakamura, Masafumi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208899/
https://www.ncbi.nlm.nih.gov/pubmed/34134073
http://dx.doi.org/10.1016/j.tranon.2021.101152
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author Koga, Satoko
Onishi, Hideya
Masuda, Shogo
Fujimura, Akiko
Ichimiya, Shu
Nakayama, Kazunori
Imaizumi, Akira
Nishiyama, Kenichi
Kojima, Masayuki
Miyoshi, Kei
Nakamura, Katsuya
Umebayashi, Masayo
Morisaki, Takashi
Nakamura, Masafumi
author_facet Koga, Satoko
Onishi, Hideya
Masuda, Shogo
Fujimura, Akiko
Ichimiya, Shu
Nakayama, Kazunori
Imaizumi, Akira
Nishiyama, Kenichi
Kojima, Masayuki
Miyoshi, Kei
Nakamura, Katsuya
Umebayashi, Masayo
Morisaki, Takashi
Nakamura, Masafumi
author_sort Koga, Satoko
collection PubMed
description 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.
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spelling pubmed-82088992021-06-28 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 Koga, Satoko Onishi, Hideya Masuda, Shogo Fujimura, Akiko Ichimiya, Shu Nakayama, Kazunori Imaizumi, Akira Nishiyama, Kenichi Kojima, Masayuki Miyoshi, Kei Nakamura, Katsuya Umebayashi, Masayo Morisaki, Takashi Nakamura, Masafumi Transl Oncol Original Research 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. Neoplasia Press 2021-06-13 /pmc/articles/PMC8208899/ /pubmed/34134073 http://dx.doi.org/10.1016/j.tranon.2021.101152 Text en © 2021 The Authors. Published by Elsevier Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Research
Koga, Satoko
Onishi, Hideya
Masuda, Shogo
Fujimura, Akiko
Ichimiya, Shu
Nakayama, Kazunori
Imaizumi, Akira
Nishiyama, Kenichi
Kojima, Masayuki
Miyoshi, Kei
Nakamura, Katsuya
Umebayashi, Masayo
Morisaki, Takashi
Nakamura, Masafumi
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208899/
https://www.ncbi.nlm.nih.gov/pubmed/34134073
http://dx.doi.org/10.1016/j.tranon.2021.101152
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