Abstract
PurposeT-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.MethodsThis 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.ResultsOf 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).ConclusionsOS 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.
Highlights
Recent studies have shown that the tumor immune system plays an important role in solid tumors microenvironment (TME)
We previously reported that programmed cell death ligand-1 (PD-L1) expression on tumor cells was related to high tumor-infiltrating lymphocytes (TILs) levels, and the combination of high TIL levels and positive PD-L1 was associated with a better prognosis in triple-negative breast cancer (TNBC) [9]
We evaluated 242 TNBC tumors with respect to the clinicopathologic data (Table 1) and CD8 and T-bet expression on TILs (Supplementary Fig. S1)
Summary
Recent studies have shown that the tumor immune system plays an important role in solid tumors microenvironment (TME). Triple-negative breast cancer (TNBC) lacking the expression of estrogen and progesterone receptors and ERBB2 is a heterogeneous tumor that encompasses several molecular subtypes of breast cancer. Because this specific subtype of TNBC includes high levels of somatic mutations [5], it is expected to benefit from a variety of immunotherapies. Many analyses of treatment for immune checkpoint blockade have made it clear that TILs play an important role in treating cancers in both adjuvant and neoadjuvant settings [6,7,8].
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