Evaluation of the prognostic value of CD3, CD8, and FOXP3 mRNA expression in early‐stage breast cancer patients treated with anthracycline‐based adjuvant chemotherapy

Abstract

BackgroundTumor‐infiltrating lymphocytes (TILs) have been shown to be of prognostic value in several cancer types. In early breast cancer, TILs have a prognostic utility, as well, especially in HER2‐positive and triple‐negative breast cancer. TILs presence is broadly associated with improved survival; however, there is controversy regarding TILs subpopulations.Patients and methodsEarly‐stage breast cancer patients treated with anthracycline‐based chemotherapy within two randomized trials were included in the study. We evaluated, by qRT‐PCR, 826 tumor tissue samples for mRNA expression of CD3, CD8, and FOXP3 for potential prognostic significance in terms of disease‐free survival (DFS) and overall survival (OS).ResultsAfter a median follow‐up of 133.0 months, 255 patients (30.9%) had died and 314 (38.0%) had disease progression. In the univariate analysis, high CD3 and CD8 mRNA expression was found to be of favorable prognostic value for DFS (P = 0.007 and P = 0.016, respectively). In multivariate analyses, the association of high CD8 mRNA expression with increased DFS was retained (HR = 0.77, 95% CI 0.60‐0.998, Wald's P = 0.048), whereas that of high CD3 mRNA expression was of marginal statistical significance (HR = 0.77, 95% CI 0.59‐1.01, P = 0.059). Moreover, a significant interaction was observed between HER2 status and CD3 mRNA expression with respect to DFS (interaction P = 0.032). In the HER2‐positive subgroup, the hazard ratio associated with high CD3 mRNA expression was of greater magnitude (HR = 0.48, 95% CI 0.30‐0.76, P = 0.002) compared with the hazard ratio presented above, for the entire cohort. No significant findings were observed for FOXP3 in terms of DFS, while none of the studied markers were of prognostic value for OS.ConclusionsHigh CD3 and CD8 mRNA expression in early‐stage breast cancer patients is of prognostic value for decreased risk of relapse and, in the future, could potentially be of importance in deciding the most appropriate therapeutic strategy in light of the recent immune‐related treatment developments.

Multiplexed Imaging Analysis of the Tumor-Immune Microenvironment Reveals Predictors of Outcome in Triple-Negative Breast Cancer

“…After Benjamini-Hochberg adjustment, there were no cell types with significant prognostic value. This includes the monocyte/neutrophil cell type 52 , the dendritic cell/monocyte cell type 53 , natural killer cells 54,55 , CD8+ T cells 24,56–60 , macrophages 61 , B cells 62 , CD4+ T cells 63,64 , and CD3+ T cells 65,66 .…”

The ITIM-Containing Receptor: Leukocyte-Associated Immunoglobulin-Like Receptor-1 (LAIR-1) Modulates Immune Response and Confers Poor Prognosis in Invasive Breast Carcinoma

“…TILS, CD3+ and CD8+ cell were associated with prognostic value in several malignancies, including BC [ 31 ]. Both FOXP3+ and PD-L1+ T cells are associated with poor patient outcome in BC [ 32 , 33 ].…”

Tumor Microenvironment: Key Players in Triple Negative Breast Cancer Immunomodulation

“…High densities of intra-tumoral Tregs and CD20 + B cells represented a good prognostic panel in TNBCs [53]. However, mRNA expression of Foxp3 by qRT-PCR in 826 breast tumor tissue samples including 84 TNBC samples, was not significantly related to disease free survival (DFS), while none of the markers studied including CD3, CD8, and Foxp3 were of prognostic value for OS [54]. This phenomenon is somewhat explained by a study showing that activation of tumor antigen-specific Tregs in the bone marrow caused the accumulation of Tregs in breast cancer tissue leading to both antitumor immunity and local immune suppression in breast cancer [55].…”