Prognostic Significance of CD20+ and CD8+ Tumor-Infiltrating Lymphocytes in Operable Triple‑Negative Breast Cancer

Abstract

Aim: This study aimed to evaluate the prognostic value of stromal TILs and their subsets (especially CD20⁺ and CD8⁺) in predicting 3-year recurrence free survival (RFS) in non-metastatic TNBC patients receiving adjuvant chemotherapy. 

Materials and methods: This prospective cohort study enrolled 109 non-metastatic TNBC patients treated with adjuvant anthracycline-taxane-based chemotherapy at Lattakia University Hospital, Lattakia, Syria. (2022–2025). TILs density was evaluated via immunohistochemistry (IHC) on pretreatment specimens using International TILs Working Group guidelines. RFS at 3 years was analyzed via Kaplan-Meier and Cox regression models.

Results: High stromal TILs (≥ 30%) were observed in 59.6% of patients and correlated with younger age (P=0.009), smaller tumors (P=0.026), and node-negative disease (P=0.017). Patients with high TILs had significantly improved 3-year RFS (72.3% vs. 40.9%, P=0.002). Elevated CD20⁺ was associated with reduced recurrence (HR: 3.86, P<0.001). Elevated CD8⁺ was associated with reduced recurrence (HR: 3.38, P<0.001). Co-elevation of CD20⁺ and CD8⁺ synergistically lowered recurrence risk by 68% (P=0.006). Multivariable analysis confirmed TILs (HR: 2.05), CD8⁺ (HR: 3.12), and CD20⁺ (HR: 2.67) as independent predictors alongside nodal status (N3: HR: 4.91), tumor size (T3-T4: HR: 1.72), and tumor grade (G3: HR: 2.18).

Conclusion: TILs subsets, particularly CD20⁺ and CD8⁺, refine prognostic stratification in early TNBC beyond conventional clinicopathologic factors.

Keywords: TNBC, tumor-infiltrating lymphocytes (TILs), adjuvant chemotherapy, CD8⁺, CD20⁺, recurrence-free survival.