Tumor-Infiltrating Lymphocytes (TILs) in Early Breast Cancer Patients: High CD3+, CD8+, and Immunoscore Are Associated with a Pathological Complete Response

Cancers (Basel). 2022 May 20;14(10):2525. doi: 10.3390/cancers14102525.

Abstract

Background: Tumor-infiltrating lymphocytes are associated with a better prognosis in early triple-negative breast cancer (TNBC). These cells can be enumerated in situ by the "Immunoscore Clinical Research" (ISCR). The original Immunoscore® is a prognostic tool that categorizes the densities of CD3+ and CD8+ cells in both the invasive margin (IM) and center of the tumor (CT) in localized colon cancer, yielding a five-tiered classification (0-4). We evaluated the prognostic potential of ISCR and pathological complete response (pCR) following neoadjuvant chemotherapy (NACT).

Methods: The cohort included 53 TNBC, 32 luminal BC, and 18 HER2-positive BC patients undergoing NACT. Pre-treatment tumor biopsies were immune-stained for CD3+ and CD8+ T-cell markers. Quantitative analysis of these cells in different tumor locations was performed using computer-assisted image analysis.

Results: The pCR rate was 44%. Univariate analysis showed that primary tumor size, estrogen-receptor negative, progesterone-receptor negative, luminal vs. HER2-positive vs. TNBC, high Ki-67, high densities (cells/mm2) of CD3 CT, CD8+ CT, CD3+ IM, and CD8+ IM cells were associated with a high pCR. ISCR was associated with pCR following NACT. A multivariate model consisting of ISCR and the significant variables from the univariate analysis showed a significant trend for ISCR; however, the low sample size did not provide enough power for the model to be included in this study.

Conclusions: These results revealed a significant prognostic role for the spatial distributions of the CD3+, and CD8+ lymphocytes, as well as the ISCR in relation to pCR following NACT.

Keywords: CD3+ lymphocytes; CD8+ lymphocytes; HER2-positive breast cancer; Ki-67; TILs; early breast cancer; luminal breast cancer.