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

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.

Roles of the immune system in cancer: from tumor initiation to metastatic progression

“…In metastasis, CTLs exert an anti-metastatic effect in bone metastasis (Bidwell et al 2012), while prospective analyses of lung and breast cancer patients established an opposite correlation between the level of circulating cancer cells and T cells in peripheral blood (Mego et al 2016;Sun et al 2017). These data extend to clinical trials reporting the therapeutic efficacy of immune checkpoint inhibition in metastatic carcinomas (Di Giacomo et al 2012;Queirolo et al 2014;Motzer et al 2015;Furudate et al 2016;Goldberg et al 2016;Pai-Scherf et al 2017).…”

Circulating tumor cell interactions with macrophages: implications for biology and treatment

“…A second type of cancer associated with high CTC counts is inflammatory breast cancer (IBC). CTC count among 147 patients with IBC reached 179 and 249 CTCs/7.5 mL blood for patients with stage III and metastatic IBC, respectively (71). IBC patients with CTCs in the peripheral blood had abnormalities in adaptive immunity that may impact tumor cell dissemination (72).…”

Next-generation Sequencing (NGS) Analysis on Single Circulating Tumor Cells (CTCs) with No Need of Whole-genome Amplification (WGA)

“…CTCs have been associated to cancer diagnosis, prognosis and are especially useful for personalized treatments with targeted therapies (10,(36)(37)(38).…”