Abstract
CTCs are involved in tumor dissemination and are an independent prognostic factor in primary and metastatic breast cancer patients. Dendritic cells (DCs) are the most efficient antigen presenting cells and are comprised of plasmacytoid-(pDC) and myeloid-(mDC) derived DC subsets. This study aimed to correlate CTC counts with the peripheral blood DC immunophenotypes and functions of inflammatory breast cancer (IBC) patients. This study included 65 IBC patients. Peripheral blood (PB) was obtained from patients prior to starting a new line of chemotherapy for CTCs enumeration by CellSearch® and DC phenotype and function by flow cytometry; the characteristics of DCs were then correlated with CTC counts and clinical outcome. Twenty-one (32.3%) patients with CTCs ≥5 had a significantly inferior overall survival (OS) compared to patients with <5 CTCs (p=0.045). In addition, patients with ≥5 CTCs had a lower percentage of mDCs capable of producing TNF-α before or after activation through the toll-like receptor (TLR), as well as a lower percentage of mDCs producing IL-12 after TLR-activation. There was a positive correlation between CTCs counts and expression of the activation (CCR7) and costimulatory (CD86) receptors on TLR-activated mDCs and pDCs, respectively. Moreover, presence of high percentage of mDC capable to produce increased levels of TNF-α was independently associated with inferior OS (p = 0.0006). An increase in the percentage of mDC producing TNF-α might induce a pro-inflammatory environment that could play a role in determining the poor clinical outcome in IBC patients and could add further prognostic value to CTCs.
Highlights
Inflammatory breast cancer (IBC) is rare but the most aggressive form of breast cancer that accounts for about 2-5% of all breast cancers [1,2,3]
We recently reported abnormalities of the innate and adaptive immunity in IBC patients with ≥1 circulating tumor cells (CTCs) per 7.5 mL of Peripheral blood (PB), consisting in lower percentages of both CD3+ and CD3+/CD4+ (T-helper) cells, as well as natural killer (NK) cells, accompanied by a higher percentage of T-reg cells in PB [28]
The proportion of patients with ≥1 CTC was lower in those with stage III disease compared to patients with metastatic IBC disease (33.3% vs 75.0%; P = 0.002)
Summary
Inflammatory breast cancer (IBC) is rare but the most aggressive form of breast cancer that accounts for about 2-5% of all breast cancers [1,2,3]. We recently reported abnormalities of the innate and adaptive immunity in IBC patients with ≥1 CTCs per 7.5 mL of PB, consisting in lower percentages of both CD3+ (pan-T) and CD3+/CD4+ (T-helper) cells, as well as NK cells, accompanied by a higher percentage of T-reg cells in PB [28]. In this translational study, we hypothesized that IBC patients with detectable CTCs in PB have lower numbers and compromised function of DCs responsible for poorer clinical outcome.
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