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

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 χ(2) = 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10549-022-06787-x.