Regarding the pre-treatment TIL profile, most studies have evaluated either lymphocytic infiltration as a whole [20]-[22] or a limited set of TIL subpopulations [12],[23]-[25] as predictors of pCR
Regarding the pre-treatment TIL profile, most studies have evaluated either lymphocytic infiltration as a whole [20]-[22] or a limited set of TIL subpopulations [12],[23]-[25] as predictors of pCR. S6. Impact of chemotherapy-induced changes (high versus low) on pCR (multivariate model including tumor phenotype). (PDF 176 KB) 13058_2014_488_MOESM2_ESM.pdf (176K) GUID:?E5DA27B2-85FF-4942-B7ED-A2702A6BF9D7 Additional file 3: Physique S2: Relative contribution of CD4 and CD8 expression to pCR in public genomic datasets. A) distribution of cases among (1S,2S,3R)-DT-061 the whole Mouse monoclonal to CRTC2 series (n?=?1001 patients; genomic datasets: GSE 16446, GSE 20194, GSE 20271, GSE 22093, GSE 23988, GSE 41998) according to high or low expression of CD4 and CD8 (cut-point: median value); pCR rates are shown for each subgroup. B) CD4 expression was associated with pCR both in the CD8 low group (0.05. NS, non significant. (TIFF 1 MB) 13058_2014_488_MOESM3_ESM.tiff (1.3M) GUID:?17A19628-D955-423F-8880-DFA313390609 Additional file 4: Figure S3: Disease free and overall survival analysis of post-NCT clusters (Y and Z) stratified by lymphocytic (CD3) infiltration. Kaplan-Meier curves showing the prognostic impact of post-NCT tumor-infiltrating immune cell profiles in tumors with low and high lymphocytic (1S,2S,3R)-DT-061 infiltration (defined as CD3 under or over P75). The difference was significant for DFS (0.05. (TIFF 1 MB) 13058_2014_488_MOESM5_ESM.tiff (1.3M) GUID:?D61DACA6-966F-4AC1-B79F-6FCAF92D0177 Authors initial file for figure 1 13058_2014_488_MOESM6_ESM.gif (92K) GUID:?6F5ADB02-5B42-43B3-8BEF-708EE0872753 Authors initial file for figure 2 13058_2014_488_MOESM7_ESM.gif (60K) GUID:?A255D2E8-2163-4F41-ADA7-5E45B6BE152F Authors initial file for physique 3 13058_2014_488_MOESM8_ESM.gif (81K) GUID:?51B704D5-D02E-473E-9AC4-FAB370AEAF5E Authors initial file for figure 4 13058_2014_488_MOESM9_ESM.gif (44K) GUID:?5762EEEF-CECC-454A-83D7-1E20F5F2F70F Abstract Introduction Tumor microenvironment immunity is usually associated with breast cancer outcome. A high lymphocytic infiltration has been associated with response to neoadjuvant chemotherapy, but the contribution to response and prognosis of immune cell subpopulations profiles in both pre-treated and post-treatment residual tumor is still unclear. Methods We analyzed (1S,2S,3R)-DT-061 pre- and post-treatment tumor-infiltrating immune cells (CD3, CD4, CD8, CD20, CD68, Foxp3) by immunohistochemistry in a series of 121 breast cancer patients homogeneously treated with neoadjuvant chemotherapy. Immune cell profiles were analyzed and correlated with response and survival. Results We recognized three tumor-infiltrating immune cell profiles, which were able to predict pathological total response (pCR) to neoadjuvant chemotherapy (cluster B: 58%, versus clusters A and C: 7%). A higher infiltration by CD4 lymphocytes was the main factor explaining the occurrence of pCR, and this association was validated in six general public genomic datasets. A higher chemotherapy effect on lymphocytic infiltration, including an inversion of CD4/CD8 ratio, was associated with pCR and with better prognosis. Analysis of the immune infiltrate in post-chemotherapy residual tumor recognized a profile (cluster Y), mainly characterized by high CD3 and CD68 infiltration, with a worse disease free survival. Conclusions Breast cancer immune cell subpopulation profiles, determined by immunohistochemistry-based computerized analysis, identify groups of patients characterized by high response (in the pre-treatment setting) and poor prognosis (in the post-treatment setting). Further understanding of the mechanisms underlying the distribution of immune cells and their changes after chemotherapy may contribute to the development of new immune-targeted therapies for breast malignancy. Electronic supplementary material The online version of this article (doi:10.1186/s13058-014-0488-5) contains supplementary material, which is available (1S,2S,3R)-DT-061 to authorized users. Introduction Neoadjuvant chemotherapy (NCT) is an progressively used therapeutic strategy for early breast malignancy. Besides its ability to (1S,2S,3R)-DT-061 induce clinical responses that allow breast-preserving surgery [1]-[3], the neoadjuvant setting is usually a formidable research tool to unveil mechanisms of resistance to treatment. Pathological total response (pCR) to NCT is currently acknowledged as a surrogate endpoint for therapeutic benefit, especially in human epidermal growth factor receptor 2 (HER2) and basal breast cancer [4]. Schedules that include sequential anthracyclines and taxanes render a higher rate of pCR, thus being the preferred neoadjuvant regimens [5],[6]. Adaptive and innate immune responses play an important role in tumor immunosurveillance, and they may limit the development.