Seroma fluid subsequent to axillary lymph node dissection for breast cancer derives from an accumulation of afferent lymph

Montalto, Erika; Mangraviti, Salvatore; Costa, Guilherme; Carrega, Paolo; Morandi, Barbara; Pezzino, Gaetana; Bonaccorsi, Irene; Cancellieri, Antonino; Mingari, Maria Cristina; Mesiti, M.; Ferlazzo, Guido; Melioli, Giovanni

doi:10.1016/j.imlet.2010.03.002

Cited by 36 publications

(30 citation statements)

References 15 publications

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“…By analyzing an accrual of human afferent lymph, we have identified leukocytes with typical DC features but that differ from myeloid APCs detectable in other human biological fluids, including circulating blood DCs and inflammatory CD14 + cells detectable in exudates. In line with these findings, previous studies reported that seroma fluids differ from exudates in both molecular features and cellular content (21), thus ruling out the possibility that seroma DCs might merely represent APCs that have been recruited because of local inflammation via routes other than lymphatic vessels. In support of the assumption that seroma DCs derive from afferent lymph, we found that HLA-DR bright seroma DCs resemble the recently described migratory DCs harbored in human lymph nodes (17,18).…”

Section: Discussionsupporting

confidence: 76%

“…Further supporting this hypothesis, we reported the presence, in seroma fluids, of large mononuclear cells partially expressing CD14 and reminiscent of veiled cells detectable in afferent lymph (5,21).…”

supporting

confidence: 72%

“…Seroma samples were collected as previously described (21), in accordance with institutional ethical guidelines. In general, needle aspiration was performed once a week and repeated as necessary.…”

Section: Samples and Cell Isolationmentioning

confidence: 99%

“…Recently, we have reported that seroma, an accrual of fluid reported after surgical procedures such as axillary lymph node dissection (19,20), is associated with an accumulation of afferent lymph drained from upstream tissues during the interval of time needed for lymphatic vessels to reanastomose with the efferent ducts after removal of lymph nodes (21). Further supporting this hypothesis, we reported the presence, in seroma fluids, of large mononuclear cells partially expressing CD14 and reminiscent of veiled cells detectable in afferent lymph (5,21).…”

mentioning

confidence: 99%

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Characterization of Human Afferent Lymph Dendritic Cells from Seroma Fluids

Morandi

Bonaccorsi

Mesiti

et al. 2013

The Journal of Immunology

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Dendritic cells (DCs) migrate from peripheral tissues to secondary lymphoid organs (SLOs) through the afferent lymph. Owing to limitations in investigating human lymph, DCs flowing in afferent lymph have not been properly characterized in humans until now. In this study, DCs present in seroma, an accrual of human afferent lymph occurring after lymph node surgical dissection, were isolated and analyzed in detail. Two main DC subsets were identified in seroma that corresponded to the migratory DC subsets present in lymph nodes, that is, CD14+ and CD1a+. The latter also included CD1abright Langerhans cells. The two DC subsets appeared to share the same monocytic precursor and to be developmentally related; both of them spontaneously released high levels of TGF-β and displayed similar T cell–activating and –polarizing properties. In contrast, they differed in the expression of surface molecules, including TLRs; in their phagocytic activity; and in the expression of proteins involved in Ag processing and presentation. It is worth noting that although both subsets were detected in seroma in the postsurgical inflammatory phase, only CD1a+ DCs migrated via afferent lymph under steady-state conditions. In conclusion, the high numbers of DCs contained in seroma fluids allowed a proper characterization of human DCs migrating via afferent lymph, revealing a continuous stream of DCs from peripheral regions toward SLOs under normal conditions. Moreover, we showed that, in inflammatory conditions, distinct subsets of DCs can migrate to SLOs via afferent lymph.

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Section: Discussionsupporting

confidence: 76%

supporting

confidence: 72%

Section: Samples and Cell Isolationmentioning

confidence: 99%

mentioning

confidence: 99%

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Characterization of Human Afferent Lymph Dendritic Cells from Seroma Fluids

Morandi

Bonaccorsi

Mesiti

et al. 2013

The Journal of Immunology

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“…The presence of NK cells in many organs raised the question of whether NK cells eventually exit the organs or terminally reside in the tissues. To address this issue, we investigated the presence of NK cells in seroma fluid, which represents an accumulation of afferent lymph (26). Lymph represents the extracellular fluid produced continuously in peripheral tissues by blood, later enriched with peripheral tissue catabolites, cells, and debris, collected in afferent lymphatic vessels, and conveyed into secondary lymphoid organs, such as LN.…”

Section: Nk Cell Subset Distribution Is Consistent With Organ-specifimentioning

confidence: 99%

CD56brightPerforinlow Noncytotoxic Human NK Cells Are Abundant in Both Healthy and Neoplastic Solid Tissues and Recirculate to Secondary Lymphoid Organs via Afferent Lymph

Carrega

Bonaccorsi

Carlo

et al. 2014

The Journal of Immunology

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As limited information is available regarding the distribution and trafficking of NK cells among solid organs, we have analyzed a wide array of tissues derived from different human compartments. NK cells were widely distributed in most solid tissues, although their amount varied significantly depending on the tissue/organ analyzed. Interestingly, the distribution appeared to be subset specific, as some tissues were preferentially populated by CD56brightperforinlow NK cells, with others by the CD56dimperforinhigh cytotoxic counterpart. Nevertheless, most tissues were highly enriched in CD56brightperforinlow cells, and the distribution of NK subsets appeared in accordance with tissue gene expression of chemotactic factors, for which receptors are differently represented in the two subsets. Remarkably, chemokine expression pattern of tissues was modified after neoplastic transformation. As a result, although the total amount of NK cells infiltrating the tissues did not significantly change upon malignant transformation, the relative proportion of NK subsets infiltrating the tissues was different, with a trend toward a tumor-infiltrating NK population enriched in noncytotoxic cells. Besides solid tissues, CD56brightperforinlow NK cells were also detected in seroma fluids, which represents an accrual of human afferent lymph, indicating that they may leave peripheral solid tissues and recirculate to secondary lymphoid organs via lymphatic vessels. Our results provide a comprehensive mapping of NK cells in human tissues, demonstrating that discrete NK subsets populate and recirculate through most human tissues and that organ-specific chemokine expression patterns might affect their distribution. In this context, chemokine switch upon neoplastic transformation might represent a novel mechanism of tumor immune escape.

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High‐dimensional single‐cell proteomics analysis identifies immune checkpoint signatures and therapeutic targets in ulcerative colitis

et al. 2019

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Immune checkpoints are regulators of immune cells and play key roles in the modulation of immune responses. The role of checkpoints in autoimmune disease is poorly understood but likely to be central since checkpoint inhibition during cancer treatment can cause autoimmunity. We generated a high‐dimensional single‐cell proteomics data set from PBMCs of healthy individuals and patients with ulcerative colitis (UC) by mass cytometry, enabling systems‐wide analyses of immune cell frequencies and cell type‐specific expression patterns of 12 immune checkpoints. Subtle but significant changes in immune cell frequencies and checkpoint expression were observed between UC patients on different treatment regimens and between patients and healthy controls. Most strikingly, UC patients showed a reduced number of peripheral NK‐cells and those cells showed an altered phenotype including increased TIGIT expression. Based on these results, we modulated NK‐cell function ex vivo through targeting of TIGIT pathway members. In summary, we describe a pattern of changes in immune cell abundance and checkpoint expression as a basis for UC patient stratification and we show modulation of a corresponding immune cell subset through checkpoint targeting. Our approach can be used for the identification of pathogenic immune cell subsets and guide target selection in autoimmunity and chronic inflammation.

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Seroma fluid subsequent to axillary lymph node dissection for breast cancer derives from an accumulation of afferent lymph

Cited by 36 publications

References 15 publications

Characterization of Human Afferent Lymph Dendritic Cells from Seroma Fluids

Characterization of Human Afferent Lymph Dendritic Cells from Seroma Fluids

CD56brightPerforinlow Noncytotoxic Human NK Cells Are Abundant in Both Healthy and Neoplastic Solid Tissues and Recirculate to Secondary Lymphoid Organs via Afferent Lymph

High‐dimensional single‐cell proteomics analysis identifies immune checkpoint signatures and therapeutic targets in ulcerative colitis

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