Immune characterization of breast cancer metastases: prognostic implications
Posted on 2018-06-22 - 05:00
Abstract Background Tumor-infiltrating lymphocytes (TILs) evaluated in primary breast cancer (BC) convey prognostic information. Limited data in the metastatic setting are available. Methods Secondary lesions from 94 BC patients, 43 triple-negative (TN) and 51 HER2-positive, were evaluated for TILs and expression of CD8, FOXP3, and PD-L1 by immunohistochemistry. Results TILs levels on metastasis were generally low (median 5%) and did not differ between TN and HER2+ tumors. Younger patients showed significantly lower TILs (p = 0.002). In HER2+ patients, TILs were higher in lung metastases as compared to other sites (p = 0.038). TILs composition was different across metastatic sites: skin metastases presented higher FOXP3 (p = 0.002) and lower CD8/FOXP3 ratio (p = 0.032). Patients treated for metastatic BC prior to biopsy had lower CD8 (overall: p = 0.005, HER2+: p = 0.011, TN: p = 0.075). In TN patients, median overall survival (OS) was 11.8 and 62.9 months for patients with low and high TILs, respectively (HR 0.29, 95%CI 0.11–0.76, log-rank p = 0.008). CD8/FOXP3 ratio was also prognostic in TN patients (median OS 8.0, 13.2, and 54.0 months in 1st, 2nd and 3th tertile, log-rank p = 0.019). Both TILs and CD8/FOXP3 ratio were independent factors at multivariate analysis. Counterintuitively, in HER2+ BC, low TILs tumors showed better prognosis (median OS 53.7 vs 39.9 months in TILs low and TILs high, not statistically significant). Conclusions Our findings indicate the relevance of TILs as prognostic biomarker for TNBC even in the advanced setting and provide novel hypothesis-generating data on potential sources of immune heterogeneity of metastatic BC.
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Dieci, Maria; Tsvetkova, Vassilena; Orvieto, Enrico; Piacentini, Federico; Ficarra, Guido; Griguolo, Gaia; et al. (2018). Immune characterization of breast cancer metastases: prognostic implications. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.4142108.v1
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AUTHORS (18)
MD
Maria Dieci
VT
Vassilena Tsvetkova
EO
Enrico Orvieto
FP
Federico Piacentini
GF
Guido Ficarra
GG
Gaia Griguolo
FM
Federica Miglietta
TG
Tommaso Giarratano
CO
Claudia Omarini
SB
Serena Bonaguro
RC
Rocco Cappellesso
CA
Camillo Aliberti
GV
Grazia Vernaci
CG
Carlo Giorgi
GF
Giovanni Faggioni
GT
Giulia Tasca
PC
Pierfranco Conte
VG
Valentina Guarneri