Prognostic impact of stromal and intratumoral CD3, CD8 and FOXP3 in adjuvantly treated breast cancer: do they add information over stromal tumor-infiltrating lymphocyte density?
- 1 August 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cancer Immunology, Immunotherapy
- Vol. 69 (8), 1549-1564
- https://doi.org/10.1007/s00262-020-02557-0
Abstract
Background Tumor-infiltrating lymphocytes (TILs) and their subsets contribute to breast cancer prognosis. We investigated the prognostic impact of CD3+, CD8+ and FOXP3+ TILs in patients with early intermediate/high-risk breast cancer treated with adjuvant anthracycline-based chemotherapy within two randomized trials conducted by our Group. Methods We examined 1011 patients (median follow-up 130.9 months) and their tumors for total, stromal (s) and intratumoral (i) CD3, CD8 and FOXP3 lymphocyte density (counts/mm(2)) on tissue-microarray cores by immunohistochemistry. Morphological sTIL density on whole H&E-stained sections was also evaluated. Results The majority of TILs were CD3+. Total CD3 and CD8, sCD3 and sCD8, iCD3 and iCD8, sFOXP3 and iFOXP3 were strongly correlated (Spearman's rho values > 0.6). High individual lymphocytic subsets and sTIL density were strongly associated with high tumor grade, higher proliferation and HER2-positive and triple-negative tumors (allpvalues < 0.001). Higher sTIL density (10% increments), high density of almost each individual marker and all-high profiles conferred favorable prognosis. However, when adjusted for sTIL density, stromal and intratumoral lymphocytic subsets lost their prognostic significance, while higher sTIL density conferred up to 15% lower risk for relapse. Independently of sTIL density, higher total CD3+ and CD8+ TILs conferred 35% and 28% lower risk for relapse, respectively. Conclusions Stromal and intratumoral CD3+, CD8+ and FOXP3+ TIL density do not seem to add prognostic information over the morphologically assessed sTIL density, which is worth introducing in routine histology reports.Funding Information
- Amgen Ltd.
- Hellenic Cooperative Oncology Group (HE TRANS_BR)
This publication has 42 references indexed in Scilit:
- Tumor-infiltrating lymphocytes, breast cancer subtypes and therapeutic efficacyOncoImmunology, 2013
- CD4+ follicular helper T cell infiltration predicts breast cancer survivalJCI Insight, 2013
- PAM50 Breast Cancer Subtyping by RT-qPCR and Concordance with Standard Clinical Molecular MarkersBMC Medical Genomics, 2012
- Differential Response of Immunohistochemically Defined Breast Cancer Subtypes to Anthracycline-Based Adjuvant Chemotherapy with or without PaclitaxelPLOS ONE, 2012
- Hallmarks of Cancer: The Next GenerationCell, 2011
- An evaluation of the clinical significance of FOXP3+ infiltrating cells in human breast cancerBreast Cancer Research and Treatment, 2010
- Foxp3 expression in human cancer cellsJournal of Translational Medicine, 2008
- Quantification of Regulatory T Cells Enables the Identification of High-Risk Breast Cancer Patients and Those at Risk of Late RelapseJournal of Clinical Oncology, 2006
- Postoperative dose-dense sequential chemotherapy with epirubicin, followed by CMF with or without paclitaxel, in patients with high-risk operable breast cancer: a randomized phase III study conducted by the Hellenic Cooperative Oncology GroupAnnals of Oncology, 2005
- Analysis of FOXP3 protein expression in human CD4+CD25+ regulatory T cells at the single-cell levelEuropean Journal of Immunology, 2005