Integrative prognostic analysis of tumor–infiltrating lymphocytes, CD8, CD20, programmed cell death-ligand 1, and tertiary lymphoid structures in patients with early-stage triple-negative breast cancer who did not receive adjuvant chemotherapy

Shu Yazaki, Tatsunori Shimoi, Masayuki Yoshida, Hitomi Sumiyoshi-Okuma, Motoko Arakaki, Ayumi Saito, Shosuke Kita, Kasumi Yamamoto, Yuki Kojima, Tadaaki Nishikawa, Maki Tanioka, Kazuki Sudo, Emi Noguchi, Takeshi Murata, Sho Shiino, Shin Takayama, Akihiko Suto, Yuichiro Ohe, Yasuhiro Fujiwara, Kan Yonemori

研究成果査読

3 被引用数 (Scopus)

抄録

Purpose: Stromal tumor-infiltrating lymphocytes (TILs) are independent prognostic factors in systemically untreated early-stage triple-negative breast cancer (TNBC). Other immune biomarkers including CD8, CD20, programmed cell death-ligand 1 (PD-L1), and tertiary lymphoid structures (TLS) are also reported to be associated with prognosis. However, whether combining other immune biomarkers with TILs would allow for further prognostic stratification is unknown. Methods: We retrospectively analyzed 125 patients with early-stage TNBC not receiving perioperative chemotherapy. Stromal TILs and TLS were evaluated on hematoxylin–eosin slides. PD-L1 expression was evaluated using the SP142 assay. CD8 and CD20 were assessed by immunohistochemistry and counted by digital pathology. Results: Immune biomarker levels were positively correlated (p < 0.001). Adding CD8 and PD-L1 to multivariable analysis including clinicopathological factors (stage and histological grade) and TILs significantly improved the prognostic model (likelihood ratio χ2 = 9.24, p = 0.01). In Cox regression analysis, high CD8 was significantly associated with better prognosis [hazard ratio (HR) 0.69, 95% confidence interval (CI) 0.48–0.98, p = 0.04], and PD-L1 positivity was significantly associated with worse prognosis (HR 4.33, 95%CI 1.57–11.99, p = 0.005). Patients with high CD8/PD–L1 (–) tumors had the most favorable prognosis [5 year invasive disease-free survival (iDFS), 100%], while patients with low CD8/PD-L1(+) tumors had the worst prognosis (5 year iDFS, 33.3%). Conclusion: CD8 and PD-L1 levels add prognostic information beyond TILs for early-stage TNBC not receiving perioperative chemotherapy. CD8–positive T cells and PD-L1 may be useful for prognostic stratification and in designing future clinical trials of TNBC.

本文言語English
ジャーナルBreast Cancer Research and Treatment
DOI
出版ステータスAccepted/In press - 2022
外部発表はい

ASJC Scopus subject areas

  • 腫瘍学
  • 癌研究

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