Abstract 5583: Innate immune profile of inflammatory breast cancer patients
Authors: Cohen Evan N. , Gao Hui , Lee Bang-Ning , Andreopoulou Eleni , Jackson Summer A. , Parker Charla A. , Tin Sanda , Galland Matthew M. , Ueno Naoto T. , Cristofanilli Massimo , Reuben James M. 
Published: February 2011

Background: Inflammatory breast cancer (IBC) is a rare but highly aggressive form of the disease but the immune profile associate with pathology and disease progression is poorly characterized. The cells of the innate immune system including natural killer (NK) and dendritic cells (DC) can establish the conditions for an adaptive response to the tumor and can actively kill tumor cells. Alternatively, the inflammatory conditions created by these cells can promote processes like metastasis and invasion. Here we report that immune activation in IBC is associated with a poor prognosis.

Methods: A total of 76 breast cancer (BC) patients starting a new line of therapy (22 IBC, 23 metastatic IBC, 8 locally advanced breast cancer, and 23 metastatic) were evaluated for immune phenotypes and cytokine synthesis by DC activated through toll-like receptors (TLR) 7 and 8.

Results: Among evaluable patients, 39 (58%) had hormone receptor positive (HR+) primary tumors, 20 (31%) were Her2 positive, and 18 (26%) were triple negative (TN). Among IBC patients, 23 (49%) were HR+, 15 (33%) were Her2+, and 14 (31%) were TN. Among non-IBC patients, 16 (73%) were HR+, 5 (22%) were Her2+, and 4 (17%) were TN. With a mean follow-up time of 7.8 months, 11 (16%) of the patients (10 IBC) died of disease.

Most strikingly, BC survivors had a higher median CD4 count than deceased patients (p = .023) and was a significant predictor of outcome (p = 0.01). CD3 and CD19 lymphocytes of BC survivors had higher expression of CXCR4 than deceased patients (p = .038 and p = .029). In contrast, survivors also had lower lymphocyte percentages of all NK sub-types including ADCC NK (p = .008), non-ADCC NK (p = .001), exhausted (p = .014) and non-exhausted NK (p = .005) than deceased patients. Although DC counts were not significantly different, the percentage of TLR-induced pDC producing IFN-α was lower in BC survivors than deceased patients (p = 0.025). Conversely, the percentage of pDC constitutively producing the anti-inflammatory cytokine IL-10 was higher in survivors compared to non-survivors (p = .007). Compared with IBC non-survivors, IBC survivors had a higher % of pDC producing IL-10 (p = 0.005) and fewer mDC producing TNF-α (p = .030) following TLR activation. With respect to antigen presentation, mDC of BC survivors had lower expressions of the co-stimulatory molecules CD40 (p= .036), CD80 (p = .013) and CD86 (p = .006) than mDC of deceased patients.

Conclusion: We observed low CD4 counts in IBC that were associated with a poor prognosis. Additionally, immune activation as evidenced by DC pro-inflammatory cytokine production, expression of costimulatory molecules, and increased NK counts was associated with poor prognosis. Together, these data suggest that the innate immune system is highly active in the late stages of disease but the adaptive response is severely compromised by factors still unknown that can contribute to the peculiar clinical presentation and aggressive features of the disease.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5583.