TY - JOUR
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
N1 - Funding Information:
Funding This study was funded by JSPS KAKENHI Grant-in-Aid for JSPS Research Fellow 18J20301 and Fukuoka Foundation for Sound Health Cancer Research Fund.
Funding Information:
The authors thank Shoko Sadatomi, Midori Kojyo and Hiroshi Fujii for their technical assistance. We thank Dr. Takashi Morisaki from Fukuoka General Cancer Center for technical support and helpful discussions. First author got Research Fellowship for Young Scientists from Japan Society for the Promotion of Science for 3?years. This work was supported in part by JSPS KAKENHI Grant-in-Aid for JSPS Research Fellow 18J20301 and Fukuoka Foundation for Sound Health Cancer Research Fund. We also thank H. Nikki March, PhD, from Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.
Funding Information:
Acknowledgements The authors thank Shoko Sadatomi, Midori Kojyo and Hiroshi Fujii for their technical assistance. We thank Dr. Takashi Morisaki from Fukuoka General Cancer Center for technical support and helpful discussions. First author got Research Fellowship for Young Scientists from Japan Society for the Promotion of Science for 3 years. This work was supported in part by JSPS KAKENHI Grant-in-Aid for JSPS Research Fellow 18J20301 and Fukuoka Foundation for Sound Health Cancer Research Fund. We also thank H. Nikki March, PhD, from Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.
Publisher Copyright:
© 2019, The Author(s).
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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U2 - 10.1007/s10549-019-05256-2
DO - 10.1007/s10549-019-05256-2
M3 - Article
C2 - 31069590
AN - SCOPUS:85065513957
SN - 0167-6806
VL - 176
SP - 569
EP - 577
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 3
ER -
