Circulating Tumor Cells (CTC) Are Associated with Defects in Adaptive Immunity in Patients with Inflammatory Breast Cancer.
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.
1. Department of Hematopathology, 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;
M
M
Mego
1. Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA;
H
H
Gao
1. Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA;
E N
EN
Cohen
1. Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA;
S
S
Anfossi
1. Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA;
A
A
Giordano
1. Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA;
T
T
Sanda
2. Department of Breast Medical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA;
T M
TM
Fouad
1. Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA;; 6. Currently at Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) - IRCCS, Meldola (FC), Italy;
U
U
De Giorgi
1. Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA;; 7. Currently at Department of Clinical Medicine and Surgery, University Federico II, Naples. Italy;
M
M
Giuliano
3. Department of Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA;
W A
WA
Woodward
2. Department of Breast Medical 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;; 8. Currently at Cancer Treatment Centers of America, Newnan, GA, USA;
R H
RH
Alvarez
2. Department of Breast Medical 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;
V
V
Valero
2. Department of Breast Medical 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;
N T
NT
Ueno
2. Department of Breast Medical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA;
G N
GN
Hortobagyi
2. Department of Breast Medical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA;; 9. Currently at Thomas Jefferson University-Kimmel Cancer Center, Philadelphia, PA, USA.
M
M
Cristofanilli
1. Department of Hematopathology, 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;
J M
JM
Reuben
Circulating tumors cells; adaptive immunity; and inflammatory breast cancer