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

Hitomi Mori, Makoto Kubo, Masaya Kai, Mai Yamada, Kanako Kurata, Hitomi Kawaji, Kazuhisa Kaneshiro, Tomofumi Osako, Reiki Nishimura, Nobuyuki Arima, Masayuki Okido, Junji Kishimoto, Yoshinao Oda, Masafumi Nakamura

Research output: Contribution to journalArticle

Abstract

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 mm2. 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.

Original languageEnglish
Pages (from-to)569-577
Number of pages9
JournalBreast Cancer Research and Treatment
Volume176
Issue number3
DOIs
Publication statusPublished - Aug 15 2019

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Triple Negative Breast Neoplasms
Lymphocytes
Survival
Tumor-Infiltrating Lymphocytes
Neoplasms
Recurrence
Confidence Intervals
T-Lymphocytes
Adjuvant Chemotherapy
T-Cell Antigen Receptor
Immunotherapy
Multivariate Analysis
Immunohistochemistry
Drug Therapy

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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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.

In: Breast Cancer Research and Treatment, Vol. 176, No. 3, 15.08.2019, p. 569-577.

Research output: Contribution to journalArticle

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. In: Breast Cancer Research and Treatment. 2019 ; Vol. 176, No. 3. pp. 569-577.
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abstract = "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 mm2. 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.",
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T1 - T-bet+ lymphocytes infiltration as an independent better prognostic indicator for triple-negative breast cancer

AU - Mori, Hitomi

AU - Kubo, Makoto

AU - Kai, Masaya

AU - Yamada, Mai

AU - Kurata, Kanako

AU - Kawaji, Hitomi

AU - Kaneshiro, Kazuhisa

AU - Osako, Tomofumi

AU - Nishimura, Reiki

AU - Arima, Nobuyuki

AU - Okido, Masayuki

AU - Kishimoto, Junji

AU - Oda, Yoshinao

AU - Nakamura, Masafumi

PY - 2019/8/15

Y1 - 2019/8/15

N2 - 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 mm2. 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.

AB - 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 mm2. 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.

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