Circulating Tumor Cells (CTC) Are Associated with Defects in Adaptive Immunity in Patients with Inflammatory Breast Cancer

M Mego, H Gao, E N Cohen, S Anfossi, A Giordano, T Sanda, T M Fouad, U De Giorgi, M Giuliano, W A Woodward, R H Alvarez, V Valero, N T Ueno, G N Hortobagyi, M Cristofanilli, J M Reuben, M Mego, H Gao, E N Cohen, S Anfossi, A Giordano, T Sanda, T M Fouad, U De Giorgi, M Giuliano, W A Woodward, R H Alvarez, V Valero, N T Ueno, G N Hortobagyi, M Cristofanilli, J M Reuben

Abstract

Background: Circulating tumor cells (CTCs) play a crucial role in tumor dissemination and are prognostic in primary and metastatic breast cancer. Peripheral blood (PB) immune cells contribute to an unfavorable microenvironment for CTC survival. This study aimed to correlate CTCs with the PB T-cell immunophenotypes and functions of patients with inflammatory breast cancer (IBC).

Methods: This study included 65 IBC patients treated at the MD Anderson Cancer Center. PB was obtained from patients prior to starting a new line of chemotherapy for CTCs enumeration by CellSearch(®), and T cell phenotype and function by flow cytometry; the results were correlated with CTCs and clinical outcome.

Results: At least 1 CTC (≥1) or ≥5 CTCs was detected in 61.5% or 32.3% of patients, respectively. CTC count did not correlate with total lymphocytes; however, patients with ≥1 CTC or ≥5 CTCs had lower percentages (%) of CD3+ and CD4+ T cells compared with patients with no CTCs or <5 CTCs, respectively. Patients with ≥1 CTC had a lower percentage of T-cell receptor (TCR)-activated CD8+ T cells synthesizing TNF-α and IFN-γ and a higher percentage of T-regulatory lymphocytes compared to patients without CTCs. In multivariate analysis, tumor grade and % CD3+ T-cells were associated with ≥1 CTC, whereas ≥5 CTC was associated with tumor grade, stage, % CD3+ and % CD4+ T cells, and % TCR-activated CD8 T-cells synthesizing IL-17.

Conclusions: IBC patients with CTCs in PB had abnormalities in adaptive immunity that could potentially impact tumor cell dissemination and initiation of the metastatic cascade.

Keywords: Circulating tumors cells; adaptive immunity; and inflammatory breast cancer.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Prognostic value of CTC (A) and combined prognostic value of CTC and TCR-activated CD8+ T cells synthesizing IFN-γ (B). Patients with “low” TCR-activated CD8+ T cells synthesizing IFN-γ and CTC ≥ 5 (group 3) had significantly worse survival (median OS = 10.5 months) compared to patients with “high” TCR-activated CD8+ T cells synthesizing IFN-γ and CTC < 5 (group 1) (median OS not reached). Patients with either “low” TCR-activated CD8+ T cells synthesizing IFN-γ and CTC < 5 (group 0) (median OS = 19.4 months) or “high” TCR-activated CD8+ T cells synthesizing IFN-γ and CTC ≥ 5 (group 4) (median OS = 24.9 months) had intermediate prognosis. TCR-activated CD8+ T cells s synthesizing IFN-γ were dichotomized as “low” or “high” based on median value of percentage of these cells in all patients.
Figure 1
Figure 1
Prognostic value of CTC (A) and combined prognostic value of CTC and TCR-activated CD8+ T cells synthesizing IFN-γ (B). Patients with “low” TCR-activated CD8+ T cells synthesizing IFN-γ and CTC ≥ 5 (group 3) had significantly worse survival (median OS = 10.5 months) compared to patients with “high” TCR-activated CD8+ T cells synthesizing IFN-γ and CTC < 5 (group 1) (median OS not reached). Patients with either “low” TCR-activated CD8+ T cells synthesizing IFN-γ and CTC < 5 (group 0) (median OS = 19.4 months) or “high” TCR-activated CD8+ T cells synthesizing IFN-γ and CTC ≥ 5 (group 4) (median OS = 24.9 months) had intermediate prognosis. TCR-activated CD8+ T cells s synthesizing IFN-γ were dichotomized as “low” or “high” based on median value of percentage of these cells in all patients.

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