Cargando…

Relationship between Microsatellite Instability, Immune Cells Infiltration, and Expression of Immune Checkpoint Molecules in Ovarian Carcinoma: Immunotherapeutic Strategies for the Future

Ovarian cancer has the worst prognosis among gynecological cancers. Thus, new ovarian cancer treatment strategies are needed. Currently, immune checkpoint inhibitors such as anti-PD-1/PD-L1 antibody are attracting attention worldwide. The Food and Drug Administration approved the use of the PD-1 ant...

Descripción completa

Detalles Bibliográficos
Autores principales: Yamashita, Hitomi, Nakayama, Kentaro, Ishikawa, Masako, Ishibashi, Tomoka, Nakamura, Kohei, Sawada, Kiyoka, Yoshimura, Yuki, Tatsumi, Nagisa, Kurose, Sonomi, Minamoto, Toshiko, Iida, Kouji, Razia, Sultana, Ishikawa, Noriyoshi, Kyo, Satoru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829575/
https://www.ncbi.nlm.nih.gov/pubmed/31623180
http://dx.doi.org/10.3390/ijms20205129
_version_ 1783465590363521024
author Yamashita, Hitomi
Nakayama, Kentaro
Ishikawa, Masako
Ishibashi, Tomoka
Nakamura, Kohei
Sawada, Kiyoka
Yoshimura, Yuki
Tatsumi, Nagisa
Kurose, Sonomi
Minamoto, Toshiko
Iida, Kouji
Razia, Sultana
Ishikawa, Noriyoshi
Kyo, Satoru
author_facet Yamashita, Hitomi
Nakayama, Kentaro
Ishikawa, Masako
Ishibashi, Tomoka
Nakamura, Kohei
Sawada, Kiyoka
Yoshimura, Yuki
Tatsumi, Nagisa
Kurose, Sonomi
Minamoto, Toshiko
Iida, Kouji
Razia, Sultana
Ishikawa, Noriyoshi
Kyo, Satoru
author_sort Yamashita, Hitomi
collection PubMed
description Ovarian cancer has the worst prognosis among gynecological cancers. Thus, new ovarian cancer treatment strategies are needed. Currently, immune checkpoint inhibitors such as anti-PD-1/PD-L1 antibody are attracting attention worldwide. The Food and Drug Administration approved the use of the PD-1 antibody pembrolizumab for solid cancers with microsatellite instability (MSI)-H or mismatch repair (MMR) deficiency in 2017. However, few studies on ovarian carcinoma have evaluated the relationship among MSI status, lymphocyte infiltration into the tumor, and the expression of immune checkpoint molecules by histologic type. We evaluated the expression of MMR proteins, tumor-infiltrating lymphocytes (CD8+), and immune checkpoint molecules (PD-L1/PD-1) by immunohistochemistry in 136 ovarian cancer patients (76, 13, 23, and 24 cases were high-grade serous, mucinous, endometrioid, and clear cell carcinoma, respectively) to investigate the effectiveness of immune checkpoint inhibitors. Only six cases (4.4%) had loss of MMR protein expression. There was no significant relationship between MSI status and age (p = 0.496), FIGO stage (p = 0.357), initial treatment (primary debulking surgery [PDS] or neoadjuvant chemotherapy) (p = 0.419), residual tumor after PDS or interval debulking surgery (p = 0.202), and expression of CD8 (p = 0.126), PD-L1 (p = 0.432), and PD-1 (p = 0.653). These results suggest that only a small number of MSI cases in ovarian cancer can be effectively treated with immune checkpoint inhibitor monotherapy. Therefore, to improve the prognosis of ovarian carcinoma, a combination therapy of immune checkpoint inhibitors and other anticancer drugs is necessary.
format Online
Article
Text
id pubmed-6829575
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-68295752019-11-18 Relationship between Microsatellite Instability, Immune Cells Infiltration, and Expression of Immune Checkpoint Molecules in Ovarian Carcinoma: Immunotherapeutic Strategies for the Future Yamashita, Hitomi Nakayama, Kentaro Ishikawa, Masako Ishibashi, Tomoka Nakamura, Kohei Sawada, Kiyoka Yoshimura, Yuki Tatsumi, Nagisa Kurose, Sonomi Minamoto, Toshiko Iida, Kouji Razia, Sultana Ishikawa, Noriyoshi Kyo, Satoru Int J Mol Sci Article Ovarian cancer has the worst prognosis among gynecological cancers. Thus, new ovarian cancer treatment strategies are needed. Currently, immune checkpoint inhibitors such as anti-PD-1/PD-L1 antibody are attracting attention worldwide. The Food and Drug Administration approved the use of the PD-1 antibody pembrolizumab for solid cancers with microsatellite instability (MSI)-H or mismatch repair (MMR) deficiency in 2017. However, few studies on ovarian carcinoma have evaluated the relationship among MSI status, lymphocyte infiltration into the tumor, and the expression of immune checkpoint molecules by histologic type. We evaluated the expression of MMR proteins, tumor-infiltrating lymphocytes (CD8+), and immune checkpoint molecules (PD-L1/PD-1) by immunohistochemistry in 136 ovarian cancer patients (76, 13, 23, and 24 cases were high-grade serous, mucinous, endometrioid, and clear cell carcinoma, respectively) to investigate the effectiveness of immune checkpoint inhibitors. Only six cases (4.4%) had loss of MMR protein expression. There was no significant relationship between MSI status and age (p = 0.496), FIGO stage (p = 0.357), initial treatment (primary debulking surgery [PDS] or neoadjuvant chemotherapy) (p = 0.419), residual tumor after PDS or interval debulking surgery (p = 0.202), and expression of CD8 (p = 0.126), PD-L1 (p = 0.432), and PD-1 (p = 0.653). These results suggest that only a small number of MSI cases in ovarian cancer can be effectively treated with immune checkpoint inhibitor monotherapy. Therefore, to improve the prognosis of ovarian carcinoma, a combination therapy of immune checkpoint inhibitors and other anticancer drugs is necessary. MDPI 2019-10-16 /pmc/articles/PMC6829575/ /pubmed/31623180 http://dx.doi.org/10.3390/ijms20205129 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yamashita, Hitomi
Nakayama, Kentaro
Ishikawa, Masako
Ishibashi, Tomoka
Nakamura, Kohei
Sawada, Kiyoka
Yoshimura, Yuki
Tatsumi, Nagisa
Kurose, Sonomi
Minamoto, Toshiko
Iida, Kouji
Razia, Sultana
Ishikawa, Noriyoshi
Kyo, Satoru
Relationship between Microsatellite Instability, Immune Cells Infiltration, and Expression of Immune Checkpoint Molecules in Ovarian Carcinoma: Immunotherapeutic Strategies for the Future
title Relationship between Microsatellite Instability, Immune Cells Infiltration, and Expression of Immune Checkpoint Molecules in Ovarian Carcinoma: Immunotherapeutic Strategies for the Future
title_full Relationship between Microsatellite Instability, Immune Cells Infiltration, and Expression of Immune Checkpoint Molecules in Ovarian Carcinoma: Immunotherapeutic Strategies for the Future
title_fullStr Relationship between Microsatellite Instability, Immune Cells Infiltration, and Expression of Immune Checkpoint Molecules in Ovarian Carcinoma: Immunotherapeutic Strategies for the Future
title_full_unstemmed Relationship between Microsatellite Instability, Immune Cells Infiltration, and Expression of Immune Checkpoint Molecules in Ovarian Carcinoma: Immunotherapeutic Strategies for the Future
title_short Relationship between Microsatellite Instability, Immune Cells Infiltration, and Expression of Immune Checkpoint Molecules in Ovarian Carcinoma: Immunotherapeutic Strategies for the Future
title_sort relationship between microsatellite instability, immune cells infiltration, and expression of immune checkpoint molecules in ovarian carcinoma: immunotherapeutic strategies for the future
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829575/
https://www.ncbi.nlm.nih.gov/pubmed/31623180
http://dx.doi.org/10.3390/ijms20205129
work_keys_str_mv AT yamashitahitomi relationshipbetweenmicrosatelliteinstabilityimmunecellsinfiltrationandexpressionofimmunecheckpointmoleculesinovariancarcinomaimmunotherapeuticstrategiesforthefuture
AT nakayamakentaro relationshipbetweenmicrosatelliteinstabilityimmunecellsinfiltrationandexpressionofimmunecheckpointmoleculesinovariancarcinomaimmunotherapeuticstrategiesforthefuture
AT ishikawamasako relationshipbetweenmicrosatelliteinstabilityimmunecellsinfiltrationandexpressionofimmunecheckpointmoleculesinovariancarcinomaimmunotherapeuticstrategiesforthefuture
AT ishibashitomoka relationshipbetweenmicrosatelliteinstabilityimmunecellsinfiltrationandexpressionofimmunecheckpointmoleculesinovariancarcinomaimmunotherapeuticstrategiesforthefuture
AT nakamurakohei relationshipbetweenmicrosatelliteinstabilityimmunecellsinfiltrationandexpressionofimmunecheckpointmoleculesinovariancarcinomaimmunotherapeuticstrategiesforthefuture
AT sawadakiyoka relationshipbetweenmicrosatelliteinstabilityimmunecellsinfiltrationandexpressionofimmunecheckpointmoleculesinovariancarcinomaimmunotherapeuticstrategiesforthefuture
AT yoshimurayuki relationshipbetweenmicrosatelliteinstabilityimmunecellsinfiltrationandexpressionofimmunecheckpointmoleculesinovariancarcinomaimmunotherapeuticstrategiesforthefuture
AT tatsuminagisa relationshipbetweenmicrosatelliteinstabilityimmunecellsinfiltrationandexpressionofimmunecheckpointmoleculesinovariancarcinomaimmunotherapeuticstrategiesforthefuture
AT kurosesonomi relationshipbetweenmicrosatelliteinstabilityimmunecellsinfiltrationandexpressionofimmunecheckpointmoleculesinovariancarcinomaimmunotherapeuticstrategiesforthefuture
AT minamototoshiko relationshipbetweenmicrosatelliteinstabilityimmunecellsinfiltrationandexpressionofimmunecheckpointmoleculesinovariancarcinomaimmunotherapeuticstrategiesforthefuture
AT iidakouji relationshipbetweenmicrosatelliteinstabilityimmunecellsinfiltrationandexpressionofimmunecheckpointmoleculesinovariancarcinomaimmunotherapeuticstrategiesforthefuture
AT raziasultana relationshipbetweenmicrosatelliteinstabilityimmunecellsinfiltrationandexpressionofimmunecheckpointmoleculesinovariancarcinomaimmunotherapeuticstrategiesforthefuture
AT ishikawanoriyoshi relationshipbetweenmicrosatelliteinstabilityimmunecellsinfiltrationandexpressionofimmunecheckpointmoleculesinovariancarcinomaimmunotherapeuticstrategiesforthefuture
AT kyosatoru relationshipbetweenmicrosatelliteinstabilityimmunecellsinfiltrationandexpressionofimmunecheckpointmoleculesinovariancarcinomaimmunotherapeuticstrategiesforthefuture