Rapoport, Bernardo LeonNayler, SimonMlecnik, BernhardSmit, TeresaHeyman, Heino MartinBouquet, IsabelleMartel, MarineGalon, JeromeBenn, Carol-AnnAnderson, Ronald2022-07-142022-07-142022-05-20Rapoport, B.L.; Nayler, S.; Mlecnik, B.; Smit, T.; Heyman, L.; Bouquet, I.; Martel, M.; Galon, J.; Benn, C.-A.; Anderson, R. Tumor-Infiltrating Lymphocytes (TILs) in Early Breast Cancer Patients: High CD3+ , CD8+ , and Immunoscore Are Associated with a Pathological Complete Response. Cancers 2022, 14, 2525. https://doi.org/10.3390/cancers14102525.2072-6694 (online)10.3390/cancers14102525https://repository.up.ac.za/handle/2263/86164BACKGROUND : 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, progesteronereceptor 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.en© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.CD3+ lymphocytesCD8+ lymphocytesEarly breast cancerHER2-positive breast cancerKi-67Luminal breast cancerTumor-infiltrating lymphocytes (TILs)Triple-negative breast cancer (TNBC)Immunoscore clinical research (ISCR)Article