J Cancer 2016; 7(9):1095-1104. doi:10.7150/jca.13098

Research Paper

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

M Mego1,5, H Gao1, EN Cohen1, S Anfossi1, A Giordano1, T Sanda1, TM Fouad2, U De Giorgi1,6, M Giuliano1,7, WA Woodward3, RH Alvarez2,4,8, V Valero2,4, NT Ueno2,4, GN Hortobagyi2, M Cristofanilli2,9, JM Reuben1,4,✉

1. Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA;
2. Department of Breast Medical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA;
3. Department of Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA;
4. Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA;
5. Currently at 2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia;
6. Currently at Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) - IRCCS, Meldola (FC), Italy;
7. Currently at Department of Clinical Medicine and Surgery, University Federico II, Naples. Italy;
8. Currently at Cancer Treatment Centers of America, Newnan, GA, USA;
9. Currently at Thomas Jefferson University-Kimmel Cancer Center, Philadelphia, PA, USA.

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

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Mego M, Gao H, Cohen E, Anfossi S, Giordano A, Sanda T, Fouad T, De Giorgi U, Giuliano M, Woodward W, Alvarez R, Valero V, Ueno N, Hortobagyi G, Cristofanilli M, Reuben J. Circulating Tumor Cells (CTC) Are Associated with Defects in Adaptive Immunity in Patients with Inflammatory Breast Cancer. J Cancer 2016; 7(9):1095-1104. doi:10.7150/jca.13098. Available from http://www.jcancer.org/v07p1095.htm