CD3+, CD4+ & CD8+ tumour infiltrating lymphocytes (TILs) are predictors of favourable survival outcome in infiltrating ductal carcinoma of breast

Abstract

Background & objectives: Tumour infiltrating lymphocytes (TILs) represent the host immune response against cancer cells associated with good or bad prognosis in different tumour types. This study was undertaken to evaluate the significance of CD3+, CD4+ and CD8+ TILs in breast cancer tissues in relation to clinico-pathological variables and survival outcome.

Methods: Immunohistochemistry (IHC) was performed with antibodies against CD3, CD4 and CD8 antigens on formalin-fixed paraffin-embedded tissue sections of 150 breast cancer patients. Intratumoural and stromal TIL counting was performed semiquantitatively.

Results: The higher CD3+, CD4+ and CD8+ intratumoural and stromal counts showed independent and direct association with good prognosis. The prognostic predictor value of intratumoural counts was higher than stromal counts. The independent associations of intratumoural and stromal counts became more prominent when adjusted with stage and grade, respectively. Among intratumoural counts, the high (++/+++) CD4+ count (OR=3.85, 95% CI=3.28-16.71, P<0.001) showed the highest survival followed by CD3+ (OR=2.70, 95% CI=1.76-8.30, P=0.001) and CD8+ (OR=2.58, 95% CI=1.55-5.86, p0 =0.001) the least when compared to respective low (+) counts. In contrast, among stromal counts, the high CD8+ count (OR=3.13, 95% CI=2.20-9.57, p0 <0.001) showed the highest survival followed by CD4+ (OR=3.02, 95% CI=2.07-8.89, p0 <0.001) and CD3+ (OR=2.45, 95% CI=1.53-6.73, p0 =0.002) the least.

Interpretation & conclusions: Our results suggest that intratumoural CD4+ and stromal CD8+ counts by immunohistochemistry may serve as an independent prognosticator for favourable outcome in breast cancer.

Fig. 1

(a) Histological section from infiltrating ductal carcinoma (IDC) breast showing intratumoural and stromal TILs (black arrows) (Hematoxylin & Eosin (HE) × 200); (b) Intratumoural and stromal CD3+ TILs in IDC (black arrows) (Immunostain ×200); (c) Intratumoural CD4+ TILs in IDC (black circle) (Immunostain × 400); (d) Stromal CD8+ TILs in IDC (black circle) (Immunostain ×400).

Fig. 2

Overall survival proportions according to CD3+ (a), CD4+ (b) and CD8+ (c) intratumoural and stromal TIL counts, respectively.