Seroma after simple mastectomy in breast cancer — the role of CD4+ T helper cells and the evidence as a oossible specific immune process

Seroma development after breast cancer surgery is the most common postoperative complication seen after mastectomy but neither its origin nor its cellular composition is known. To investigate the assumption of immunological significance, one of the first aims of this pilot study is to describe the cellular content of collected seroma fluids and its corresponding serum in patients with simple mastectomy after needle aspiration, as well as the serum of healthy controls. The content of red blood cells (RBC) was measured by haemato-counter analyses, and the lymphocyte identification/quantification was conducted by flow cytometry analyses in seroma fluid (SFl) and the sera of patients (PBp) as well as controls (PBc). Significantly lower numbers of RBCs were measured in SFl. Cytotoxic T cells are significantly reduced in SFl, whereas T helper (Th) cells are significantly enriched compared to PBp. Significantly higher numbers of Th2 cells were found in SFl and PBp compared to PBc. The exact same pattern is seen when analyzing the Th17 subgroup. In conclusion, in contrast to healthy controls, significantly higher Th2 and Th17 cell subgroup-mediated immune responses were measured in seroma formations and were further confirmed in the peripheral blood of breast cancer (including DCIS) patients after simple mastectomy. This could lead to the assumption of a possible immunological cause for the origin of a seroma

Elderly and patients with large breast volume have an increased risk of seroma formation after mastectomy — results of the SerMa pilot study

The collective of the SerMa pilot study included 100 cases of primary breast cancer or Carcinoma in situ who had undergone a mastectomy procedure with or without reconstruction of the breast using an implant or expander at Augsburg University Hospital between 12/2019 and 12/2022. The study aimed to investigate possible causes of seroma formation; reported here are the clinicopathological correlations between seroma formation and tumor biology and surgical procedures. Seroma occurred significantly more often in patients with older age (median patient age in cases with seroma was 73 years vs. 52 years without seroma; p < 0.001). In addition, patients with larger mastectomy specimen were significantly more likely to develop seroma (median ablation weight in cases with seroma 580 g vs. 330 g without seroma; p < 0.001). Other significant parameters for seroma formation were BMI (p = 0.005), grading (p = 0.015) and tumor size (p = 0.036). In addition, with insertion of implant or expander, a seroma occurred significantly less frequently (p < 0.001). In a binary logistic regression, age in particular was confirmed as a significant risk factor. In contrast, tumor biological characteristics, number of lymph nodes removed or affected showed no significant effect on seroma formation. The present study shows the need for patient education about the development of seroma in particular in older patients and patients with large breast volumes within the preoperative surgical clarification. These clinicopathological data support the previously published results hypothesizing that seroma formation is related to autoimmune/inflammatory processes and will be tested on a larger collective in the planned international multicenter SerMa study

Th2/Th17 cell associated cytokines found in seroma fluids after breast cancer surgery

Purpose The development of a seroma after breast cancer surgery is a common postoperative complication seen after simple mastectomy and axillary surgery. We could recently demonstrate that breast cancer patients undergoing a simple mastectomy with subsequent seroma formation developed a T-helper cell increase within the aspirated fluid measured by flow cytometry. The same study revealed a Th2 and/or a Th17 immune response in peripheral blood and seroma fluid of the same patient. Based on these results and within the same study population, we now analyzed the Th2/Th17 cell associated cytokine content as well as the best known clinical important cytokine IL-6. Methods Multiplex cytokine measurements (IL-4, IL-5, IL-13, IL-10, IL-17, and IL-22) were done on 34 seroma fluids (Sf) after fine needle aspiration of patients who developed a seroma after a simple mastectomy. Serum of the same patient (Sp) and that of healthy volunteers (Sc) were used as controls. Results We found the Sf to be highly cytokine rich. Almost all analyzed cytokines were significantly higher in abundance in the Sf compared to Sp and Sc, especially IL-6, which promotes Th17 differentiation as well as suppresses Th1 differentiation in favor of Th2 development. Conclusion Our Sf cytokine measurements reflect a local immune event. In contrast, former study results on T-helper cell populations in both Sf and Sp tend to demonstrate a systemic immune process

Association between body fat distribution and B-lymphocyte subsets in peripheral blood

Abstract Background Obesity is associated with chronic low-grade inflammation, which is underpinned by the presence of elevated levels of circulating proinflammatory cytokines in obese individuals. Due to the close relationship between adipose tissue and the immune system, it can be speculated that the accumulation of fat may influence the frequency and phenotype of lymphocyte populations. The aim of our study was to investigate whether body fat distribution is associated with B lymphocyte composition in peripheral blood. We examined the association between visceral (VAT) and total body fat (TBF) and the frequencies of B-cell subsets in 238 subjects over a period of up to one year using random intercept models. B lymphocyte subsets were determined by fluorescence-based flow cytometry. Results Inverse associations were found between body fat measurements and plasma blasts, memory B cells, and IgM − IgD − cells. VAT, but not TBF, was positively associated with naive CD19 cells. In our analyses, both VAT and TBF showed positive associations with IgD only B cells. Conclusions In conclusion, body fat accumulation seems to be associated with a lower proportion of antibody-secreting plasma blasts and memory cells and an increasing amount of partially anergic, naive CD19 cells

MicroRNA-223 dose levels fine tune proliferation and differentiation in human cord blood progenitors and acute myeloid leukemia

A precise understanding of the role of miR-223 in human hematopoiesis and in the pathogenesis of acute myeloid leukemia (AML) is still lacking. By measuring miR-223 expression in blasts from 115 AML patients, we found significantly higher miR-223 levels in patients with favorable prognosis, whereas patients with low miR-223 expression levels were associated with worse outcome. Furthermore, miR-223 was hierarchically expressed in AML subpopulations, with lower expression in leukemic stem cell-containing fractions. Genetic depletion of miR-223 decreased the leukemia initiating cell (LIC) frequency in a myelomonocytic AML mouse model, but it was not mandatory for rapid-onset AML. To relate these observations to physiologic myeloid differentiation, we knocked down or ectopically expressed miR-223 in cord-blood CD34+ cells using lentiviral vectors. Although miR-223 knockdown delayed myeloerythroid precursor differentiation in vitro, it increased myeloid progenitors in vivo following serial xenotransplantation. Ectopic miR-223 expression increased erythropoiesis, T lymphopoiesis, and early B lymphopoiesis in vivo. These findings broaden the role of miR-223 as a regulator of the expansion/differentiation equilibrium in hematopoietic stem and progenitor cells where its impact is dose- and differentiation-stage-dependent. This also explains the complex yet minor role of miR-223 in AML, a heterogeneous disease with variable degree of myeloid differentiation

MicroRNA-223 dose levels fine tune proliferation and differentiation in human cord blood progenitors and acute myeloid leukemia

A precise understanding of the role of miR-223 in human hematopoiesis and in the pathogenesis of acute myeloid leukemia (AML) is still lacking. By measuring miR-223 expression in blasts from 115 AML patients, we found significantly higher miR-223 levels in patients with favorable prognosis, whereas patients with low miR-223 expression levels were associated with worse outcome. Furthermore, miR-223 was hierarchically expressed in AML subpopulations, with lower expression in leukemic stem cell–containing fractions. Genetic depletion of miR-223 decreased the leukemia initiating cell (LIC) frequency in a myelomonocytic AML mouse model, but it was not mandatory for rapid-onset AML. To relate these observations to physiologic myeloid differentiation, we knocked down or ectopically expressed miR-223 in cord-blood CD34(+) cells using lentiviral vectors. Although miR-223 knockdown delayed myeloerythroid precursor differentiation in vitro, it increased myeloid progenitors in vivo following serial xenotransplantation. Ectopic miR-223 expression increased erythropoiesis, T lymphopoiesis, and early B lymphopoiesis in vivo. These findings broaden the role of miR-223 as a regulator of the expansion/differentiation equilibrium in hematopoietic stem and progenitor cells where its impact is dose- and differentiation-stage-dependent. This also explains the complex yet minor role of miR-223 in AML, a heterogeneous disease with variable degree of myeloid differentiation