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T-bet(+) lymphocytes infiltration as an independent better prognostic indicator for triple-negative breast cancer

PURPOSE: T-box transcription factor 21 (T-bet), which is the master regulator of effector T-cell activation, is derived by stimulation of T-cell receptors. In this study, we focused on T-bet and examined the function of activated T cells. METHODS: This study included 242 patients with primary triple...

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Autores principales: Mori, Hitomi, Kubo, Makoto, Kai, Masaya, Yamada, Mai, Kurata, Kanako, Kawaji, Hitomi, Kaneshiro, Kazuhisa, Osako, Tomofumi, Nishimura, Reiki, Arima, Nobuyuki, Okido, Masayuki, Kishimoto, Junji, Oda, Yoshinao, Nakamura, Masafumi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586701/
https://www.ncbi.nlm.nih.gov/pubmed/31069590
http://dx.doi.org/10.1007/s10549-019-05256-2
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author Mori, Hitomi
Kubo, Makoto
Kai, Masaya
Yamada, Mai
Kurata, Kanako
Kawaji, Hitomi
Kaneshiro, Kazuhisa
Osako, Tomofumi
Nishimura, Reiki
Arima, Nobuyuki
Okido, Masayuki
Kishimoto, Junji
Oda, Yoshinao
Nakamura, Masafumi
author_facet Mori, Hitomi
Kubo, Makoto
Kai, Masaya
Yamada, Mai
Kurata, Kanako
Kawaji, Hitomi
Kaneshiro, Kazuhisa
Osako, Tomofumi
Nishimura, Reiki
Arima, Nobuyuki
Okido, Masayuki
Kishimoto, Junji
Oda, Yoshinao
Nakamura, Masafumi
author_sort Mori, Hitomi
collection PubMed
description PURPOSE: T-box transcription factor 21 (T-bet), which is the master regulator of effector T-cell activation, is derived by stimulation of T-cell receptors. In this study, we focused on T-bet and examined the function of activated T cells. METHODS: This study included 242 patients with primary triple-negative breast cancer (TNBC) who underwent resection without neoadjuvant chemotherapy between January 2004 and December 2014. The immunohistochemistry scoring for CD8 and T-bet expression on tumor-infiltrating lymphocytes (TILs) was defined as ≥ 30 per 6.25 × 10(−3) mm(2). RESULTS: Of the 242 TNBC cases, CD8 was positively expressed in 127 (52.5%) tumors, and T-bet was positively expressed in 67 (27.7%) tumors. T-bet expression was significantly correlated with CD8 expression (p < 0.0001). Patients with T-bet(+) tumors had longer overall survival (OS) compared with patients with T-bet(−) tumors (p = 0.047). The combination of CD8(+) and T-bet(+) was associated with a better recurrence-free survival (RFS) and OS compared to CD8(+)/T-bet(−) tumors (p = 0.037 and p = 0.024, respectively). Adjuvant chemotherapy provided significantly greater benefit to patients with T-bet(+) tumors (p = 0.031 for RFS, p = 0.0003 for OS). Multivariate analysis revealed that T-bet expression on TILs was an independent and positive prognostic indicator (HR = 0.36, 95% confidence interval (CI) 0.12–0.94, p = 0.037 for RFS, HR = 0.30, 95% CI 0.07–0.95, p = 0.039 for OS). CONCLUSIONS: OS was significantly improved for patients with high T-bet-expressing TILs in TNBC. Thus, T-bet may be a predictive indicator for survival and various immunotherapy strategies in TNBC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10549-019-05256-2) contains supplementary material, which is available to authorized users.
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spelling pubmed-65867012019-07-05 T-bet(+) lymphocytes infiltration as an independent better prognostic indicator for triple-negative breast cancer Mori, Hitomi Kubo, Makoto Kai, Masaya Yamada, Mai Kurata, Kanako Kawaji, Hitomi Kaneshiro, Kazuhisa Osako, Tomofumi Nishimura, Reiki Arima, Nobuyuki Okido, Masayuki Kishimoto, Junji Oda, Yoshinao Nakamura, Masafumi Breast Cancer Res Treat Preclinical Study PURPOSE: T-box transcription factor 21 (T-bet), which is the master regulator of effector T-cell activation, is derived by stimulation of T-cell receptors. In this study, we focused on T-bet and examined the function of activated T cells. METHODS: This study included 242 patients with primary triple-negative breast cancer (TNBC) who underwent resection without neoadjuvant chemotherapy between January 2004 and December 2014. The immunohistochemistry scoring for CD8 and T-bet expression on tumor-infiltrating lymphocytes (TILs) was defined as ≥ 30 per 6.25 × 10(−3) mm(2). RESULTS: Of the 242 TNBC cases, CD8 was positively expressed in 127 (52.5%) tumors, and T-bet was positively expressed in 67 (27.7%) tumors. T-bet expression was significantly correlated with CD8 expression (p < 0.0001). Patients with T-bet(+) tumors had longer overall survival (OS) compared with patients with T-bet(−) tumors (p = 0.047). The combination of CD8(+) and T-bet(+) was associated with a better recurrence-free survival (RFS) and OS compared to CD8(+)/T-bet(−) tumors (p = 0.037 and p = 0.024, respectively). Adjuvant chemotherapy provided significantly greater benefit to patients with T-bet(+) tumors (p = 0.031 for RFS, p = 0.0003 for OS). Multivariate analysis revealed that T-bet expression on TILs was an independent and positive prognostic indicator (HR = 0.36, 95% confidence interval (CI) 0.12–0.94, p = 0.037 for RFS, HR = 0.30, 95% CI 0.07–0.95, p = 0.039 for OS). CONCLUSIONS: OS was significantly improved for patients with high T-bet-expressing TILs in TNBC. Thus, T-bet may be a predictive indicator for survival and various immunotherapy strategies in TNBC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10549-019-05256-2) contains supplementary material, which is available to authorized users. Springer US 2019-05-08 2019 /pmc/articles/PMC6586701/ /pubmed/31069590 http://dx.doi.org/10.1007/s10549-019-05256-2 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Preclinical Study
Mori, Hitomi
Kubo, Makoto
Kai, Masaya
Yamada, Mai
Kurata, Kanako
Kawaji, Hitomi
Kaneshiro, Kazuhisa
Osako, Tomofumi
Nishimura, Reiki
Arima, Nobuyuki
Okido, Masayuki
Kishimoto, Junji
Oda, Yoshinao
Nakamura, Masafumi
T-bet(+) lymphocytes infiltration as an independent better prognostic indicator for triple-negative breast cancer
title T-bet(+) lymphocytes infiltration as an independent better prognostic indicator for triple-negative breast cancer
title_full T-bet(+) lymphocytes infiltration as an independent better prognostic indicator for triple-negative breast cancer
title_fullStr T-bet(+) lymphocytes infiltration as an independent better prognostic indicator for triple-negative breast cancer
title_full_unstemmed T-bet(+) lymphocytes infiltration as an independent better prognostic indicator for triple-negative breast cancer
title_short T-bet(+) lymphocytes infiltration as an independent better prognostic indicator for triple-negative breast cancer
title_sort t-bet(+) lymphocytes infiltration as an independent better prognostic indicator for triple-negative breast cancer
topic Preclinical Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586701/
https://www.ncbi.nlm.nih.gov/pubmed/31069590
http://dx.doi.org/10.1007/s10549-019-05256-2
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