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Purpose N6-methyladenosine (m6A) is the most frequent type of messenger RNA (mRNA) modification and is implicated in diverse physiological processes. The procedure of m6A RNA modification is regulated by a dynamic interaction of writers (METTL3, METTL4, METTL14, WTAP, KIAA1429), erasers (FTO, ALKBH5), and readers (HNRNPA2B1, HNRNPC, YTHDC1, YTHDC1, YTHDF1-3). In the oncological context, alterations in m6A were identified to be critically involved in tumorigenesis, proliferation, angiogenesis, and drug resistance across diverse cancer entities including endometrial cancer (EC). Methods In this study, we comprehensively examined the protein expression of m6A writers, readers and erasers by immunohistochemical staining in a cohort of N = 65 EC patients. Protein expression data were analyzed with regard to clinical outcomes. Results We identified enhanced protein expression levels of METTL3, METTL14, FTO, HNRNPA2B1, and HNRNPC, respectively to be of prognostic value and linked to a shortened overall survival in EC. Conclusion Overall, our study points toward dysregulated m6A modification in EC and its possibility to serve as a promising prognostic biomarker.

ObjectivesBenign leiomyomas are the most common uterine tumors. In contrast, uterine leiomyosarcomas are malignancies with a poor prognosis due to difficulties in early diagnosis and inappropriate surgical treatment. Most often they are diagnosed incidentally after surgery performed for treatment of leiomyoma. As the appropriate surgical treatment is crucial for survival of the patient, there is a high demand to predict leiomyosarcoma pre-operatively. Available scoring systems to discriminate leiomyoma from leiomyosarcoma are based on retrospective studies with limited numbers of patients and are not implemented in routine clinical practice.MethodsThe aim of our study was to evaluate a recently published score—the pre-operative leiomyosarcoma (pLMS) score—to determine whether it would have been predictive of leiomyosarcoma in 177 patients from the NOGGO-REGSA study, a German register of histologically proven gynecological sarcoma detected during routine clinical investigation.ResultsThe threshold of the pLMS score for ‘leiomyosarcoma not probable’ (< −3) failed for 7.5% of the patients and the threshold ‘indicator for leiomyosarcoma’ (>+1) was true for 39.1% of the patients. 53.4% of the patients were attributed to the group ‘additional investigations are recommended’ (−3 to +1). The most relevant parameters in our analysis were suspicious sonography and rapid growth, but neither have been quantitatively defined.ConclusionIn our validation cohort, the pLMS score seems not to be a reliable tool to predict leiomyosarcoma and therefore we do not recommend its clinical implementation to identify leiomyosarcoma.

Purpose Vulvar squamous cell carcinoma (VSCC) is a rare malignancy of the female genital tract with increasing incidence rates. Etiologically, HPV-dependent and HPV-independent VSCC are distinguished. Surgical treatment and/or radiotherapy represent the therapeutic mainstay for localized disease. For recurrent or metastatic VSCC, treatment options are limited. Research has identified trophoblast cell surface antigen 2 (TROP-2) to be broadly expressed across different tumor entities. The aim of the present study was to systematically investigate the expression of TROP-2 in VSCC. Methods TROP-2 protein expression was investigated by immunohistochemistry in a cohort comprising n = 103 patients with primary VSCC. A four-tier scoring system (0: no staining, 1 + : low staining, 2 + : moderate staining, 3 + : high staining) was applied for quantification of protein expression. For further analyses, two groups (low TROP-2 expression: 0/1 + ; high TROP-2 expression: 2 + /3 +) were generated. The entire study cohort, as well as HPV-dependent and HPV-independent VSCC were considered separately. Results In the entire VSCC study cohort, TROP-2 expression was present in 97.1% of all cases (n = 100) with 74.8% displaying high TROP-2 expression (2 + /3 +). Only 2.9% of tumors showed absent TROP-2 expression. Of note, all HPV-dependent VSCC (n = 18) demonstrated high TROP-2 expression (2 + /3 +). In the subgroup of HPV-independent VSCC (n = 70), high TROP-2 expression was associated with favorable clinical outcomes based on log rank test and univariate cox analysis. Conclusion TROP-2 protein expression is of prognostic value in HPV-independent VSCC. The broad expression of TROP-2 in VSCC indicates the TROP-2 directed ADC Sacituzumab govitecan as a potential new therapeutic strategy for VSCC patients.

Background: The Cancer Genome Atlas (TCGA) network (United States National Cancer Institute) identified four molecular endometrial cancer (EC) subtypes using an extensive multi-method approach. The aim of this study was to determine the four TCGA EC molecular subtypes using a single-method whole-exome sequencing (WES)-based approach provided by MH Guide (Molecular Health, Heidelberg, Germany). Methods: WES and clinical data of n = 232 EC patients were obtained from TCGA. The four TCGA EC molecular subtypes designated as (i) Mutated Polymerase ε (POLE), (ii) Microsatellite Instability (MSI), (iii) Copy Number (CN) low and, (iv) CN-high were determined using the MH Guide software. The prognostic value of the subtypes determined by MH Guide were compared with the TCGA classification. Results: Analysis of WES data using the MH Guide software led to the precise identification of the four EC molecular subtypes analogous to the TCGA classification. Both approaches displayed high concordance in terms of prognostic significance. Conclusions: The multi-method-based TCGA EC molecular subtypes can reliably be reproduced by the single-method-based MH Guide approach. The easy-to-implement single-method MH Guide approach represents a promising diagnostic tool.

Purpose Cervical cancer (CC) is caused by a persistent high-risk human papillomavirus (hrHPV) infection. The cervico-vaginal microbiome may influence the development of (pre)cancer lesions. Aim of the study was (i) to evaluate the new CC screening program in Germany for the detection of high-grade CC precursor lesions, and (ii) to elucidate the role of the cervico-vaginal microbiome and its potential impact on cervical dysplasia. Methods The microbiome of 310 patients referred to colposcopy was determined by amplicon sequencing and correlated with clinicopathological parameters. Results Most patients were referred for colposcopy due to a positive hrHPV result in two consecutive years combined with a normal PAP smear. In 2.1% of these cases, a CIN III lesion was detected. There was a significant positive association between the PAP stage and Lactobacillus vaginalis colonization and between the severity of CC precursor lesions and Ureaplasma parvum. Conclusion In our cohort, the new cervical cancer screening program resulted in a low rate of additional CIN III detected. It is questionable whether these cases were only identified earlier with additional HPV testing before the appearance of cytological abnormalities, or the new screening program will truly increase the detection rate of CIN III in the long run. Colonization with U. parvum was associated with histological dysplastic lesions. Whether targeted therapy of this pathogen or optimization of the microbiome prevents dysplasia remains speculative.

Background: To analyze clinical, pathological and immunohistochemical correlates of survival in vaginal cancer patients. Methods: Retrospective analysis of primary vaginal cancer patients, treated at the Department of Gynecology and Gynecological Oncology of the University Hospital Bonn between 2007 and 2021. Results: The study cohort comprised 22 patients. The median age was 63 years (range: 32–87 years). Squamous cell histology was present in 20 patients. Five-year OS in Stage I, II, III and IV was 100%, 56.25%, 0% and 41.67%, respectively (p = 0.147). Five-year DFS was 100%, 50%, 0% and 20.83%, respectively (p = 0.223). The 5-year OS was significantly reduced in the presence of nodal metastasis (p = 0.004), lymphangiosis (p = 0.009), hemangiosis (p = 0.002) and an age above 64 years (p = 0.029). Positive p 16 staining was associated with significantly improved OS (p = 0.010). Tumoral and immune cell PD-L1 staining was positive in 19 and in 16 patients, respectively, without significant impact on OS; 2 patients with metastastic disease are long-term survivors treated with either bevacizumab or pembrolizumab. Conclusion: P16 expression, absence of lymph- or hemangiosis, nodal negative disease and an age below 64 years show improved survival rates in PVC. Tumoral PD-L1 expression as well as PD-L1 expression on immune cells is frequent in PVC, without impacting survival. Within our study cohort, long-term survivors with recurrent PVC are treated with anti-VEGF and immunotherapy.

The aim of this study was to analyze the predictive and prognostic value of the peritoneal cancer index (PCI) with regard to complete cytoreduction and clinical outcomes in patients with high-grade serous ovarian cancer.In a cohort comprising 188 patients with high-grade serous ovarian cancer, the PCI was retrospectively assessed. Clinical factors and perioperative complications were analyzed according to different PCI groups. Five-year disease-free survival (DFS) and overall survival (OS) were calculated based on the Kaplan-Meier Log rank analysis. Receiver operating characteristic (ROC) analysis was applied to detect associations of PCI and complete cytoreduction. Multivariate survival analysis was performed by Cox proportional hazards model.In our study, the PCI was predictive of complete cytoreduction (ROC analysis; AUC 0.8227). In patients with optimal cytoreduction, higher PCI scores were associated with poorer 5-year OS (p0.001) and 5-year DFS (p0.001). Complications (G1-G5) were significantly more frequent in patients with PCI scores9 (p=0.0023). Five-year OS was reduced in patients with severe complications compared to patients with none or mild complications (30.88% versus 51.01%; p=0.001). There were significant OS (p0.001) and DFS (p0.001) differences between patients with none or mild versus severe complications following complete cytoreduction within the PCI subgroups (PCI: 9-11, PCI: 12-18, PCI18).The PCI score showed high predictability for complete cytoreduction and was associated with clinical outcomes. In presence of severe complications, higher PCI scores were associated with poorer survival. Hence, in patients with high tumor load, the prevention of severe perioperative complications is of utmost importance in all cases where complete cytoreduction is deemed to be feasible.

There is growing scientific evidence for the crucial role of post-transcriptional RNA modifications in carcinogenesis, progression, metastasis, and drug resistance across various cancer entities. N6-methyladenosine (m6A) is the most abundant type of RNA modification. m6A is coordinated by a dynamic interplay of ‘writers’ (METTL3, METTL4, METTL14, WTAP, KIAA1429), ‘erasers’ (FTO, ALKBH5), and ‘readers’ (HNRNPA2B1, HNRNPC, YTHDC1, YTHDC1, YTHDF1-3). In this study, we comprehensively examined protein and mRNA expression levels of m6A writers, readers, and erasers in two cervical cancer (CC) cohorts (UHB CC cohort, N = 118; TCGA CC cohort, N = 307) with regard to clinical outcomes. In the UHB CC cohort, high protein expression levels of METTL14 (p = 0.016), WTAP (p = 0.007), KIAA1439 (p < 0.001), ALKBH5 (p < 0.001), HNRNPC (p = 0.012), YTHDC1 (p < 0.001), and YTHDF3 (p = 0.004) were significantly associated with a shorter overall survival (OS). In the TCGA CC cohort, mRNA expression levels of METTL14 (p = 0.012), WTAP (p = 0.041), KIAA1429 (p = 0.016), and YTHDC1 (p = 0.026) showed prognostic values. However, after correction for multiple testing, statistical significance remained only for m6A protein expression levels (q < 0.1). Our study points towards dysregulated m6A modification in CC. Hence, m6A might serve as a promising prognostic biomarker and therapeutical target in CC.

Fetal growth restriction is strongly associated with impaired placentation and abnormal uteroplacental blood flow. Nitric oxide donors such as pentaerythritol tetranitrate are strong vasodilators and protect the endothelium. Recently, we demonstrated in a randomized controlled pilot study a 38% relative risk reduction for the development of fetal growth restriction or perinatal death following administration of pentaerythritol tetranitrate to pregnant women at risk, identified by impaired uterine perfusion at midgestation. Results of this monocenter study prompted the hypothesis that pentaerythritol tetranitrate might have an effect in pregnancies with compromised placental function as a secondary prophylaxis.This study aimed to test the hypothesis that the nitric oxide donor pentaerythritol tetranitrate reduces fetal growth restriction and perinatal death in pregnant women with impaired placental perfusion at midgestation in a multicenter trial.In this multicenter, randomized, double-blind, placebo-controlled trial, 2 parallel groups of pregnant women presenting with a mean uterine artery pulsatility index95th percentile at 19+0 to 22+6 weeks of gestation were randomized to 50-mg Pentalong or placebo twice daily. Participants were assigned to high- or low-risk groups according to their medical history before randomization was performed block-wise with a fixed block length stratified by center and risk group. The primary efficacy endpoint was the composite outcome of perinatal death or development of fetal growth restriction. Secondary endpoints were neonatal and maternal outcome parameters.Between August 2017 and March 2020, 317 participants were included in the study and 307 were analyzed. The cumulative incidence of the primary outcome was 41.1% in the pentaerythritol tetranitrate group and 45.5% in the placebo group (unadjusted relative risk, 0.90; 95% confidence interval, 0.69-1.17; adjusted relative risk, 0.90; 95% confidence interval, 0.69-1.17; P=.43). Secondary outcomes such as preterm birth (unadjusted relative risk, 0.73; 95% confidence interval, 0.56-0.94; adjusted relative risk, 0.73; 95% confidence interval, 0.56-0.94; P=.01) and pregnancy-induced hypertension (unadjusted relative risk, 0.65; 95% confidence interval, 0.46-0.93; adjusted relative risk, 0.65; 95% confidence interval, 0.46-0.92; P=0.01) were reduced.Our study failed to show an impact of pentaerythritol tetranitrate on the development of fetal growth restriction and perinatal death in pregnant women with impaired uterine perfusion at midgestation. Pentaerythritol tetranitrate significantly reduced secondary outcome parameters such as the incidence of preterm birth and pregnancy-induced hypertension in these pregnancies.

Increased concentrations of interleukin 1 (IL-1) in the cerebrospinal fluid and serum of patients with Alzheimer disease (AD) reduced phagocytic capacity point to an inflammatory activation of mononuclear phagocytes in AD. Interleukin 1 receptors (IL-1R) and the macrophage scavenger receptor I (MSRI) are important players in IL-1 signaling and phagocytosis. In 20 patients with AD and 17 controls, IL-1RI, IL-1RII, and MSRI were assessed on peripheral blood mononuclear cells by flow cytometry. IL-1β, soluble IL-1 receptors, and IL-1R antagonist (IL-1Ra) were measured by enzyme-linked immunosorbent assay. The fraction of IL-1RI+ monocytes was increased by 10% and the expression of MSRI was reduced by 12% in AD. A 3.6% increased fraction of IL-1RI+ lymphocytes was accompanied by a 6.1% reduced expression of IL-1RII. The IL-1RI on monocytes and lymphocytes discriminated patients with AD with an accuracy of 0.79 and 0.75, respectively. The IL-1Ra was elevated in AD. Changes in the expression of IL-1 receptors and MSRI on peripheral blood cells fit to the concept of a proinflammatory state of the peripheral immune system. However, the observed differences are not strong enough to suggest their application as biomarkers for AD.

Femoral nerve palsy and meralgia paresthetica following gynecologic cancer surgery are rare, but severe and long lasting. Here, we aimed to study their incidence, severity, possible risk factors and its time to remission. Between January 2008 and December 2017 976 gynecologic cancer patients were identified in our institutional database receiving surgery. Complete patient charts were reviewed retrospectively. Possible risk factors were analyzed by Fisher’s exact test. 441 (45.18%) out 976 were treated for Ovarian cancer. In total 23 patients were identified with a postoperative neurological leg disorder. A femoral nerve palsy was present in 15 patients (1.5%) and a meralgia paresthetica in 8 patients (0.82%). Three patients showed both disorders. Duration of surgery (p = 0.0000), positioning during surgery (p = 0.0040), femoral artery catheter (p = 0.0051), prior chemotherapy (p = 0.0007), nicotine abuse (p = 0.00456) and prior polyneuropathy (p = 0.0181) showed a significant association with a postoperative femoral nerve palsy. Nicotine abuse (p = 0.0335) and prior chemotherapy (p = 0.0151) were significant for the development of a meralgia paresthetica. Long lasting surgery, patient positioning and femoral arterial catheter placement are risk factors for a postoperative femoral nerve palsy in gynecologic cancer surgery. Polyneuropathy, nicotine abuse, and prior chemotherapy are predisposing risk factors for a femoral nerve palsy and a meralgia paresthetica. A resolution of symptoms is the rule for both disorders within different time schedules.

Background: High grade serous ovarian cancer (HGSC), the most common and aggressive type of ovarian cancer, is nearly always driven by TP53 mutations, which can be detected in uterine lavages using ultra-deep duplex sequencing. While this finding supports the development of a uterine lavage assay for early HGSC detection, age-related TP53 mutations compromise specificity. The goal of this study was to thoroughly characterize the nature of TP53 mutations identified in uterine lavage of women with and without HGSC to better understand TP53 clonal evolution during aging and to determine its association to HGSC. Methods: Uterine lavages were collected preoperatively in 54 “average-risk” women undergoing gynecological surgery for suspicious masses (34 women ultimately had HGSC, 20 were cancer free) and in 98 “high-risk” women undergoing risk-reducing salpingo-oopherectomy (17 were found to have HGSC or serous tubal intraepithelial carcinomas (STICs), 81 were cancer-free). Ultra-deep (>10,000x), ultra-accurate sequencing of TP53 was performed on uterine lavage DNA using duplex sequencing. Tumors and STICs were also duplex sequenced to determine TP53 tumor-driving mutations. The frequency of TP53 mutations and large TP53 mutant clones (those found in >2 duplex reads) was compared between women with and without HGSC. Results: The tumor-specific TP53 mutation was detected in 53% of lavages from average-risk women with HGSC and in 22% of lavages from high-risk women with HGSC/STICs. As in prior studies, TP53 biological background mutations were identified in nearly all women and their frequency was age-related. TP53 background mutations, however, were more abundant in women with prior chemotherapy, regardless of their cancer status or age. In women without prior chemotherapy and without high-risk of HGSC, having HGSC was associated with a significantly higher frequency of large TP53 mutant clones (p=0.007) and large TP53 mutant clones containing pathogenic mutations (p=0.007) or TP53 mutations commonly found in cancer (p=0.001). Interestingly, women at high risk of HGSC also carried high frequency of large and pathogenic TP53 mutant clones in lavage, even in those cases in which cancer or STICs were not identified. Conclusions: Ultra-sensitive duplex sequencing enabled detection of a patient’s HGSC or STIC driver mutations, respectively, in about half and a quarter of uterine lavages. However, of even greater interest, we observed a significant excess of large and pathogenic TP53 mutant clones in lavages of women with HGSC that were not present in the tumor. These results indicate that TP53 somatic evolution is associated with HGSC development and suggest that the measurement of TP53 mutant clones in uterine lavages harbors value as a predictor of ovarian cancer risk. Citation Format: Rosana Risques, Thomas H. Smith, Zachary K. Norgaard, Roniz Katz, Fang Yin Lo, Elizabeth K. Schmidt, Jacob E. Higgins, Martin Filipits, Intidhar Labidi-Galy, David Cibula, Lukáš Dostálek, Gabriel Jelenek, Magdalena Plch, Jiří Bouda, Alexander Mustea, Mateja Condic, Sabine Grill, Noreen Gleeson, Peter Oppelt, Gunda Pristauz-Telsnigg, Adriaan Vanderstichele, Siel Obrecht, Adam Rosenthal, Paul Speiser, Jesse Salk. TP53 field defects in uterine fluid are associated with ovarian cancer risk [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr PR005.

This abstract is being presented as a short talk in the scientific program. A full abstract is available in the Proffered Abstracts section (PR005) of the Conference Proceedings. Citation Format: Rosana Risques, Thomas H. Smith, Zachary K. Norgaard, Roniz Katz, Fang Yin Lo, Elizabeth K. Schmidt, Jacob E. Higgins, Martin Filipits, Intidhar Labidi-Galy, David Cibula, Lukáš Dostálek, Gabriel Jelenek, Magdalena Plch, Jiří Bouda, Alexander Mustea, Mateja Condic, Sabine Grill, Noreen Gleeson, Peter Oppelt, Gunda Pristauz-Telsnigg, Adriaan Vanderstichele, Siel Obrecht, Adam Rosenthal, Paul Speiser, Jesse Salk. TP53 field defects in uterine fluid are associated with ovarian cancer risk [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr A008.

Vulvar cancer is rare but incidence rates are increasing due to an aging population and higher frequencies of young women being affected. In locally advanced, metastatic or recurrent disease prognosis is poor and new treatment modalities are needed. Immune checkpoint blockade of the PD-1/PD-L1 pathway is one of the most important advancements in cancer therapy in the last years. The clinical relevance of PD-L1 expression in vulvar cancer, however, has not been studied so far. We determined PD-L1 expression, numbers of CD3+ T cells, CD20+ B cells, CD68+ monocytes/macrophages, Foxp3+ regulatory T cells and CD163+ tumor-associated macrophages by immunohistochemistry in 103 patients. Correlation analysis with clinicopathological parameters was undertaken; the cause-specific outcome was modeled with competing risk analysis; multivariate Cox regression was used to determine independent predictors of survival. Membranous PD-L1 was expressed in a minority of tumors, defined by HPV-negativity. Its presence geographically correlated with immunocyte-rich regions of cancer islets and was an independent prognostic factor for poor outcome. Our data support the notion that vulvar cancer is an immunomodulatory tumor that harnesses the PD-1/PD-L1 pathway to induce tolerance. Accordingly, immunotherapeutic approaches might have the potential to improve outcome in patients with vulvar cancer and could complement conventional cancer treatment.

Background Elevated concentrations of circulating testosterone are present in hyperreactio luteinalis (HL), a pregnancy-specific, self-limited condition. HL is associated with maternal virilization in about 30% of cases. The correlation between testosterone levels and maternal virilization has not yet been quantified. Our aim was to identify a testosterone cut-off level which may allow to predict maternal virilization. Methods A literature research was performed. Publications were chosen if serum testosterone concentrations and presence or absence of maternal virilization was mentioned. Additionally, we report serial levels of steroids analyzed by Liquid chromatography–tandem mass spectrometry (LC–MS/MS) in one case of HL managed at our institution. Results In all, 31 cases fulfilled the search criteria. We found significant overlap between testosterone levels in asymptomatic women and women with signs of virilization (range 6.2–37.3 nmol/l and 13.7–197.5 nmol/l, respectively). The method applied for testosterone analysis was mentioned in three reports only. Peak serum testosterone concentration in our case was 120.3 nmol/l. Conclusion From the available data, maternal virilization in HL cannot be predicted by the level of circulating testosterone. However, comparability of results is hampered by the analytical methods applied. LC–MS/MS should preferably be used for reporting concentrations of circulating testosterone.

Amyloid-β (Aβ) peptides are the main components of the plaques found in the brains of patients with Alzheimer’s disease. However, Aβ peptides are also detectable in secretory compartments and peripheral blood contains a complex mixture of more than 40 different modified and/or N- and C-terminally truncated Aβ peptides. Recently, anti-infective properties of Aβ peptides have been reported. Here, we investigated the interaction of Aβ peptides of different lengths with various bacterial strains and the yeast Candida albicans. The amyloidogenic peptides Aβ1-42, Aβ2-42, and Aβ3p-42 but not the non-amyloidogenic peptides Aβ1-40 and Aβ2-40 bound to microbial surfaces. As observed by immunocytochemistry, scanning electron microscopy and Gram staining, treatment of several bacterial strains and Candida albicans with Aβ peptide variants ending at position 42 (Aβx-42) caused the formation of large agglutinates. These aggregates were not detected after incubation with Aβx-40. Furthermore, Aβx-42 exerted an antimicrobial activity on all tested pathogens, killing up to 80% of microorganisms within 6 h. Aβ1-40 only had a moderate antimicrobial activity against C. albicans. Agglutination of Aβ1-42 was accelerated in the presence of microorganisms. These data demonstrate that the amyloidogenic Aβx-42 variants have antimicrobial activity and may therefore act as antimicrobial peptides in the immune system.

Abnormal accumulations of amyloid-β (Aβ)-peptides are one of the pathological hallmarks of Alzheimer’s disease (AD). The precursor of the Aβ-peptides, the amyloid precursor protein (APP), is also found in peripheral blood cells, but its function in these cells remains elusive. We previously observed that mononuclear phagocytes release Aβ-peptides during activation and phagocytosis, suggesting a physiologic role in inflammatory processes. Here, we show that supplementing the media with soluble N-terminally truncated Aβ(2–40) and Aβ(2–42) as well as Aβ(1–42) induced the phagocytosis of polystyrene particles (PSPs) by primary human monocytes. If the PSPs were pre-incubated with Aβ-peptides, phagocytosis was induced by all tested Aβ-peptide species. N-terminally truncated Aβ(x–42) induced the phagocytosis of PSPs significantly more effectively than did Aβ(x–40). Similarly, the phagocytosis of Escherichia coli by GM-CSF- and M-CSF-elicited macrophages as well as microglia was particularly facilitated by pre-incubation with N-terminally truncated Aβ(x–42). The proinflammatory polarization of monocytes was indicated by the reduced MSRI expression and IL-10 secretion after phagocytosis of PSPs coated with Aβ(1–42), Aβ(2–42) and Aβ(3p–42). Polarization of the macrophages by GM-CSF reduced the phagocytic activity, but it did not affect the capabilities of Aβ-peptides to opsonize prey. Taken together, Aβ-peptides support phagocytosis as soluble factors and act as opsonins. Differential effects among the Aβ-peptide variants point to distinct mechanisms of interaction among monocytes/macrophages, prey and Aβ-peptides. A proinflammatory polarization induced by the phagocytosis of Aβ-peptide coated particles may provide a model for the chronic inflammatory reaction and sustained plaque deposition in AD.