Abstract P1-10-14: Focus on tumor infiltrating lymphocytes (TIL’s): High levels of spatially positioned CD3 and CD8 cells and high immunoscores are significantly associated with pathological complete responses in triple-negative breast cancer patients
Authors: Rapoport Bernardo Leon , Nayler Simon , Galon Jerome , Mlecnik B , Smit Teresa , Barnard-Tidy Jacqui , Fugon Aurelie , Martel Marine , Van Eeden Ronwyn I , Anderson Ronald , Benn Carol 
Published: March 2020

Abstract
Background: The presence of high levels of tumor infiltrating lymphocytes (TIL’s) has been associated with better prognosis in early triple-negative breast cancer (TNBC). The Immunoscore is a prognostic tool, which categorizes the densities of CD3 and CD8 cells in both invasive margins (IM) and the center of the tumor (CT) yielding a five-tiered classification (0-4). High immunoscores have been reported to predict improved outcomes in patients (pts) with colorectal cancer. Methods: The final retrospective report to be presented at the meeting will evaluate the immunoscore in 106 breast cancer (BC) patients undergoing neo-adjuvant chemotherapy. The current analysis include the results of the first 63 pts (TNBC=35, Luminal=20, Her2+=8) who received treatment with anthracycline and/or taxane and/or trastuzumab-based neo-adjuvant chemotherapy. Results: Pre-treatment tumor samples were immune-stained for T-cell (CD3, CD8) markers and quantitative analysis of the immune cells was carried out using a computer-assisted image analysis in different tumor locations. Results: A pathological complete response (pCR) was documented in 57%, 63% and 10% of TNBC, Her2-positive and luminal pts respectively. T-cell densities were significantly higher for TNBC pts compared to non-TNBC pts. A high density (more than 800mm2) of CD3 and CD8 positive T-cells in the CT was associated with higher pCR (CD8 CT: 69% vs. 16%, p = 0.00002) (CD3 CT: 57% vs. 14%, p=0.00015). Analysis of CD3 and CD8 in the IM (more than 500mm2) was also significant for an association with pCR (CD8 IM: 68% vs. 23%, p = 0.002) (CD3 IM: 68% vs. 16%, p=0.0005). In subgroup analyses, TNBC high density (more than 500mm2) of CD3 CT: 72% vs. 20%, p = 0.004 and CD8 CT: 78% vs. 35%, p = 0.001 was also significant for pCR. The immunoscore was also positively correlated with pCR (P=0.0002), and with clinical response (CR, PR, PD) (P=0.002). High immunoscore pts were at low risk of relapse, with 5-year TTR rates of 87.5 % (CI, 67-100 %) as compared to 54.9 % (CI, 29.6-100 %) in low immunoscore pts (HR=4.8 (CI 1.7-13.5), P&lt;0.03). Conclusion: The results of this ongoing study show a significant prognostic and potentially predictive role for the immunoscore in BC pts, particularly in the TNBC subset.
Citation Format: Bernardo Leon Rapoport, Simon Nayler, Jerome Galon, B Mlecnik, Teresa Smit, Jacqui Barnard-Tidy, Aurelie Fugon, Marine Martel, Ronwyn I Van Eeden, Ronald Anderson, Carol Benn. Focus on tumor infiltrating lymphocytes (TIL’s): High levels of spatially positioned CD3 and CD8 cells and high immunoscores are significantly associated with pathological complete responses in triple-negative breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-10-14.