Total Synthesis of a PSGL-1 Glycopeptide Analogue for Targeted Inhibition of P-Selectin.

The high affinity interaction between P-selectin glycoprotein ligand-1 (PSGL-1) and P-selectin is mediated by a multimotif glycosulfopeptide (GSP) recognition domain consisting of clustered tyrosine sulfates and a Core 2 O-glycan terminated with sialyl LewisX (C2-O-sLeX). These distinct GSP motifs are much more common than previously appreciated within a wide variety of functionally important domains involved in protein-protein interactions. However, despite the potential of GSPs to serve as tools for fundamental studies and prospects for drug discovery, their utility has been limited by the absence of chemical schemes for synthesis on scale. Herein, we report the total synthesis of GSnP-6, an analogue of the N-terminal domain of PSGL-1, and potent inhibitor of P-selectin. An efficient, scalable, hydrogenolysis-free synthesis of C2-O-sLeX-Thr-COOH was identified by both convergent and orthogonal one-pot assembly, which afforded this crucial building block, ready for direct use in solid phase peptide synthesis (SPPS). C2-O-sLeX-Thr-COOH was synthesized in 10 steps with an overall yield of 23% from the 4-O,5-N oxazolidinone thiosialoside donor. This synthesis represents an 80-fold improvement in reaction yield as compared to prior reports, achieving the first gram scale synthesis of SPPS ready C2-O-sLeX-Thr-COOH and enabling the scalable synthesis of GSnP-6 for preclinical evaluation. Significantly, we established that GSnP-6 displays dose-dependent inhibition of venous thrombosis in vivo and inhibits vaso-occlusive events in a human sickle cell disease equivalent microvasculature-on-a-chip system. The insights gained in formulating this design strategy can be broadly applied to the synthesis of a wide variety of biologically important oligosaccharides and O-glycan bearing glycopeptides.

Arbeitsgemeinschaft Gynäkologische Onkologie Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2024.

Introduction: Each year the interdisciplinary AGO (Arbeitsgemeinschaft Gynäkologische Onkologie, German Gynecological Oncology Group) Breast Committee on Diagnosis and Treatment of Breast Cancer provides updated state-of-the-art recommendations for early and metastatic breast cancer. Methods: The updated evidence-based treatment recommendations for early and metastatic breast cancer have been released in March 2024. Results and Conclusion: This paper concisely captures the updated recommendations for early breast cancer chapter by chapter.

Arbeitsgemeinschaft Gynäkologische Onkologie Recommendations for the Diagnosis and Treatment of Patients with Locally Advanced and Metastatic Breast Cancer: Update 2024.

The Breast Committee of the Arbeitsgemeinschaft Gynäkologische Onkologie (German Gynecological Oncology Group, AGO) presents the 2024 update of the evidence-based recommendations for the diagnosis and treatment of patients with locally advanced and metastatic breast cancer.

The Safety and Efficacy of the Combination of Sacituzumab Govitecan and Palliative Radiotherapy-A Retrospective Multi-Center Cohort Study.

Sacituzumab govitecan (SG) is a new treatment option for patients with metastatic triple-negative and hormone receptor-positive, HER2-negative breast cancer. This antibody-drug conjugate is currently approved as monotherapy. Palliative radiotherapy is frequently used to treat symptomatic metastases locally. Concurrent use of SG and irradiation was excluded in clinical trials of SG, and there are currently limited published data. We report here a systematic review, as well as a retrospective multi-center study of 17 patients with triple-negative breast cancer who received concurrent SG and radiotherapy. In these patients, concurrent use was found to be efficient, safe and well tolerated. There were no apparent differences in moderate or severe acute toxicity according to the timing of SG administration.

Genome-wide association analyses of ovarian cancer patients undergoing primary debulking surgery identify candidate genes for residual disease.

Survival from ovarian cancer depends on the resection status after primary surgery. We performed genome-wide association analyses for resection status of 7705 ovarian cancer patients, including 4954 with high-grade serous carcinoma (HGSOC), to identify variants associated with residual disease. The most significant association with resection status was observed for rs72845444, upstream of MGMT, in HGSOC (p = 3.9 × 10-8). In gene-based analyses, PPP2R5C was the most strongly associated gene in HGSOC after stage adjustment. In an independent set of 378 ovarian tumours from the AGO-OVAR 11 study, variants near MGMT and PPP2R5C correlated with methylation and transcript levels, and PPP2R5C mRNA levels predicted progression-free survival in patients with residual disease. MGMT encodes a DNA repair enzyme, and PPP2R5C encodes the B56γ subunit of the PP2A tumour suppressor. Our results link heritable variation at these two loci with resection status in HGSOC.

Locally Advanced Adenocarcinoma of the Esophagus: Is Esophagectomy Associated with Improved Overall Survival?

BACKGROUND: Esophagectomy in locally advanced esophageal adenocarcinoma is challenging and carries risk. The value of esophagectomy in locally advanced esophageal adenocarcinoma is not well-defined. STUDY DESIGN: The National Cancer Database was used to identify patients with cT4 esophageal adenocarcinoma from 2004 to 2020. Multivariable regression was used to identify factors associated with use of esophagectomy. Cox modeling was used to identify factors associated with all-cause mortality. Patients undergoing esophagectomy were 1:1 propensity score-matched to patients treated nonsurgically. Kaplan-Meier analysis was used to compare 5-year overall survival (OS). RESULTS: A total of 3,703 patients met inclusion criteria. Of those, 541 (15%) underwent esophagectomy, and 3,162 (85%) did not. Age 65 years or less (adjusted odds ratio [aOR] 1.69, 95% CI 1.33 to 2.14), White race (aOR 2.98, 95% CI 2.24 to 3.96), treatment in academic centers (aOR 1.64, 95% CI 1.33 to 2.02), private insurance (aOR 1.88, 95% CI 1.50 to 2.36), and tumors less than 6 cm (aOR 1.86, 95% CI 1.44 to 2.40) were associated with use of esophagectomy. Government of lack of insurance (hazard ratio [HR] 1.23, 95% CI 1.12 to 1.35), income <$46,000 (HR 1.11, 95% CI 1.03 to 1.20), treatment in nonacademic centers (HR 1.16, 95% CI 1.07 to 1.25), Charlson-Deyo Comorbidity Index 1 or more (HR 1.22, 95% CI 1.12 to 1.32), and tumors 6 cm or more (HR 1.20, 95% CI 1.09 to 1.32) were associated with risk of all-cause mortality. Esophagectomy (HR 0.50, 95% CI 0.44 to 0.56) and systemic therapy (HR 0.40, 95% CI 0.37 to 0.43) were associated with decreased risk of all-cause mortality. Patients undergoing esophagectomy had higher rates of 5-year OS (27.4% vs 13.2%, p < 0.0001) and longer median OS (24.71 vs 10.09 months, p < 0.0001). Among cT4b patients, those who underwent esophagectomy had higher rates of 5-year OS (24.5% vs 12.3%, p < 0.0001) and longer median OS (25.53 vs 11.01 months, p < 0.0001). CONCLUSIONS: In cT4 esophageal adenocarcinoma, esophagectomy is associated with improved rates of 5-year OS compared with nonsurgical treatment.

Combined analysis of secreted proteins and glycosylation identifies prognostic features in cholangiocarcinoma.

Secreted proteins are overexpressed in cholangiocarcinoma (CCA) and actively involved in promoting metastatic spread. Many of these proteins possess one or more sites of glycosylation and their various glycoforms have potential utility as prognostic or diagnostic biomarkers. To evaluate the effects of secretome glycosylation on patient outcome, we elucidated the glycosylation patterns of proteins secreted by parental and metastatic CCA cells using liquid chromatography-mass spectrometry. Our analysis showed that the secretome of CCA cells was dominated by fucosylated and fucosialylated glycoforms. Based on the glycan and protein profiles, we evaluated the combined prognostic significance of glycosyltransferases and secretory proteins. Significantly, genes encoding fucosyltransferases and sialyltransferases showed favorable prognostic effects when combined with secretory protein-coding gene expression, particularly thrombospondin-1. Combining these measures may provide improved risk assessment for CCA and be used to indicate stages of disease progression.

Nanoparticle-based nanocomposite coatings with postprocessing for enhanced antimicrobial capacity of polymeric film.

Bacterial adhesion and biofilm formation on surfaces pose a significant risk of microbial contamination and chronic diseases, leading to potential health complications. To mitigate this concern, the implementation of antibacterial coatings becomes paramount in reducing pathogen propagation on contaminated surfaces. To address this requirement, our study focuses on developing cost-effective and sustainable methods using polymer composite coatings. Copper and titanium dioxide nanoparticles were used to assess their active antimicrobial functions. After coating the surface with nanoparticles, four different combinations of two postprocessing treatments were performed. Intense pulsed light was utilized to sinter the coatings further, and plasma etching was applied to manipulate the physical properties of the nanocomposite-coated sheet surface. Bacterial viability was comparatively analyzed at four different time points (0, 30, 60, and 120 min) upon contact with the nanocomposite coatings. The samples with nanoparticle coatings and postprocessing treatments showed an above-average 84.82% mortality rate at 30 min and an average of 89.77% mortality rate at 120 min of contact. In contrast, the control sample, without nanoparticle coatings and postprocessing treatments, showed a 95% microbe viability after 120 min of contact. Through this study, we gained critical insights into effective strategies for preventing the spread of microorganisms on high-touch surfaces, thereby contributing to the advancement of sustainable antimicrobial coatings.

Fragmented care in localized pancreatic cancer: Is commission on cancer accreditation associated with improved overall survival?

BACKGROUND: Prior studies of fragmentation of care in pancreatic cancer have not adjusted for indicators of hospital quality such as Commission on Cancer accreditation. The effect of fragmentation of care has not been well defined. METHODS: We queried the National Cancer Database to identify patients undergoing pancreaticoduodenectomy and distal pancreatectomy with perioperative systemic therapy for clinical stages I-III pancreatic cancer between 2006 and 2019. Patients who received systemic therapy at a center different than the center performing surgery were categorized as having fragmentation of care. Patients having fragmentation of care were further categorized on the basis of whether (fragmentation of care Commission on Cancer) or not (fragmentation of care non-Commission on Cancer) systemic therapy was administered at a facility accredited by the Commission on Cancer. RESULTS: A total of 11,732 patients met inclusion criteria; 5,668 (48.3%) underwent fragmentation of care, and 3,426 (29.2%) fragmentation of care non-Commission on Cancer. Patients undergoing fragmentation of care non-Commission on Cancer were less likely to receive neoadjuvant systemic therapy than those undergoing fragmentation of care Commission on Cancer or non-fragmented care (27.7% vs 40.1% vs 36.8%, P < .001). On Cox analysis, advanced age, comorbid disease, node-positive disease, and facility type were associated with risk of overall survival. Fragmentation of care was not (adjusted hazard ratio = 0.99, 95% confidence interval [0.94-1.06], P = .8). On Kaplan-Meier analysis, there were no significant differences in 5-year overall survival between treatment cohorts. CONCLUSION: In patients undergoing fragmentation of care for localized pancreatic cancer, those treated with systemic therapy in Commission on Cancer accredited facilities are more likely to be given neoadjuvant therapy but demonstrate no significant improvement in survival relative to those undergoing non-fragmented care or those undergoing fragmentation of care but receiving systemic therapy in nonaccredited facilities.

Fragmented care, Commission on Cancer accreditation, and overall survival in patients receiving surgery and chemotherapy for esophageal cancer.

BACKGROUND: Increasing regionalization for esophagectomy for cancer may lead patients to travel for surgery at one institution and receive chemotherapy at another closer to home. We explore the effects on survival for care fragmentation, the Commission on Cancer status of secondary institutions providing chemotherapy, and the type of institution performing surgery. METHODS: We queried the National Cancer Database to identify all patients who underwent esophagectomy for esophageal cancer and received perioperative chemotherapy between 2006 and 2019. Patients were divided into single-center care, fragmented-to-Commission on Cancer care, or fragmented-to-non-Commission on Cancer care. We identified associations using multivariable logistic regression, Kaplan-Meier survival analyses, and Cox proportional hazards models. RESULTS: A total of 18,502 patients met the criteria for inclusion: 8,290 (44.8%) received single-center care; 3,414 (18.5%) fragmented-to-Commission on Cancer care; and 6,798 (36.4%) fragmented-to-non-Commission on Cancer care. Fragmented care was more likely in White patients (adjusted odds ratio = 1.25; P < .001) and in patients nonadjacent to a metropolitan area (adjusted odds ratio = 1.36; P < .001). Overall survival was equivalent between single-center and fragmented care, but undergoing an esophagectomy at an academic center was associated with improved survival (adjusted hazard ratio = 0.82; P = .016). In patients with an esophagectomy at a nonacademic center, overall survival was best if perioperative chemotherapy was administered at Commission on Cancer-accredited facilities compared with chemotherapy at fragmented-to-non-Commission on Cancer centers (P = .022). CONCLUSION: Most of the esophageal cancer care in the US is fragmented at multiple institutions. When care is fragmented, it is most commonly at non-Commission on Cancer centers for perioperative chemotherapy. Overall survival is best when esophagectomy is performed at an academic center, and perioperative therapy is administered at Commission on Cancer-accredited facilities.

Clinical stage T2N0M0 rectal adenocarcinoma: Is radical resection associated with improved overall survival in patients with low-risk histology?

BACKGROUND: Prior studies evaluating the efficacy of local excision compared to radical resection in the treatment of rectal adenocarcinoma lacked sufficient power to identify differences in outcomes for patients with cT2 disease but low-risk histopathology. We compared the outcomes of local excision and radical resection for low-risk histopathology and high-risk histology of patients with cT2N0M0 rectal adenocarcinoma to assess their outcomes. METHODS: We queried the National Cancer Database for patients presenting with cT2N0M0 rectal adenocarcinoma between 2004 and 2019 and categorized them as low-risk histopathology or high-risk histology. We used the Cox proportional hazards model to identify factors associated with the risk of all-cause mortality. We 1:1 propensity-matched patients who underwent local excision to patients who underwent radical resection and used the Kaplan-Meier method to compare overall survival for matched cohorts. RESULTS: Of the 4,446 patients selected, we classified 1,206 (27%) as high-risk histology and 3,240 (73%) as low-risk histopathology. Among the patients with high-risk histology, 121 (10%) underwent local excision and 1,085 (90%) underwent radical resection. Among the patients with low-risk histopathology, 340 (10%) underwent local excision and 2,900 (90%) radical resections. Whereas radical resection was associated with decreased risk of all-cause mortality and increased overall survival for patients with high-risk histology, it was not for patients with low-risk histopathology. CONCLUSION: The overall survival of patients with low-risk histopathology with cT2N0M0 rectal adenocarcinoma who undergo local excision is similar to those of patients with low-risk histopathology who undergo radical resection, suggesting local excision is a reasonable approach for these patients. In contrast, radical resection provides a significant survival advantage for patients with high-risk histology and should remain their treatment of choice.

Does commission on cancer (CoC) accreditation mitigate the effect of care fragmentation on clinical outcome in localized rectal cancer?

BACKGROUND: Studies of fragmented care (FC) in rectal cancer have not adjusted for indicators of hospital quality and may misrepresent the effects of FC. METHODS: We queried the National Cancer Database to identify patients undergoing care for clinical stage II and III rectal adenocarcinoma between 2006 and 2019. Those undergoing FC were sub-categorized based on whether (FC CoC) or not (FC non-CoC) they received systemic therapy at CoC accredited facilities. RESULTS: 44,339 patients met inclusion criteria; 23,921 (54 â€‹%) underwent FC, 16,929 (71 â€‹%) FC non-CoC. Differences in utilization of neoadjuvant therapy (92.3 â€‹% vs 89.7 â€‹% vs 89.5 â€‹%, p â€‹< â€‹0.01) and 5-year overall survival (76.1 vs 75.5 vs 74.1 %, p â€‹< â€‹0.01) between treatment cohorts were marginal. CONCLUSION: In patients undergoing multimodality therapy for rectal cancer, care fragmentation is not associated with long-term clinical outcome. Decisions regarding where these patients go for systemic therapy may be safely made on the basis of ease of access.

Clinical effectiveness and safety of olaparib in BRCA-mutated, HER2-negative metastatic breast cancer in a real-world setting: final analysis of LUCY.

PURPOSE: The interim analysis of the phase IIIb LUCY trial demonstrated the clinical effectiveness of olaparib in patients with germline BRCA-mutated (gBRCAm), human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (mBC), with median progression-free survival (PFS) of 8.11 months, which was similar to that in the olaparib arm of the phase III OlympiAD trial (7.03 months). This prespecified analysis provides final overall survival (OS) and safety data. METHODS: The open-label, single-arm LUCY trial of olaparib (300 mg, twice daily) enrolled adults with gBRCAm or somatic BRCA-mutated (sBRCAm), HER2-negative mBC. Patients had previously received a taxane or anthracycline for neoadjuvant/adjuvant or metastatic disease and up to two lines of chemotherapy for mBC. RESULTS: Of 563 patients screened, 256 (gBRCAm, n = 253; sBRCAm, n = 3) were enrolled. In the gBRCAm cohort, median investigator-assessed PFS (primary endpoint) was 8.18 months and median OS was 24.94 months. Olaparib was clinically effective in all prespecified subgroups: hormone receptor status, previous chemotherapy for mBC, previous platinum-based chemotherapy (including by line of therapy), and previous cyclin-dependent kinase 4/6 inhibitor use. The most frequent treatment-emergent adverse events (TEAEs) were nausea (55.3%) and anemia (39.2%). Few patients (6.3%) discontinued olaparib owing to a TEAE. No deaths associated with AEs occurred during the study treatment or 30-day follow-up. CONCLUSION: The LUCY patient population reflects a real-world population in line with the licensed indication of olaparib in mBC. These findings support the clinical effectiveness and safety of olaparib in patients with gBRCAm, HER2-negative mBC. CLINICAL TRIAL REGISTRATION: Clinical trials registration number: NCT03286842.

Anti-Inflammatory Artificial Extracellular Vesicles with Notable Inhibition of Particulate Matter-Induced Skin Inflammation and Barrier Function Impairment.

Particulate matter (PM) exposure disrupts the skin barrier, causing cutaneous inflammation that may eventually contribute to the development of various skin diseases. Herein, we introduce anti-inflammatory artificial extracellular vesicles (AEVs) fabricated through cell extrusion using the biosurfactant PEGylated mannosylerythritol lipid (P-MEL), hereafter named AEVP-MEL. The P-MEL has anti-inflammatory abilities with demonstrated efficacy in inhibiting the secretion of pro-inflammatory mediators. Mechanistically, AEVP-MEL enhanced anti-inflammatory response by inhibiting the mitogen-activated protein kinase (MAPK) pathway and decreasing the release of inflammatory mediators such as reactive oxygen species (ROS), cyclooxygenase-2 (COX-2), and pro-inflammatory cytokines in human keratinocytes. Moreover, AEVP-MEL promoted increased expression levels of skin barrier proteins (e.g., involucrin, IVL) and water-proteins (e.g., aquaporin 3, AQP3). In vivo studies revealed that repeated PM exposure to intact skin resulted in cutaneous inflammatory responses, including increased skin thickness (hyperkeratosis) and mast cell infiltration. Importantly, our data showed that the AEVP-MEL treatment significantly restored immune homeostasis in the skin affected by PM-induced inflammation and enhanced the intrinsic skin barrier function. This study highlights the potential of the AEVP-MEL in promoting skin health against PM exposure and its promising implications for the prevention and treatment of PM-related skin disorders.

AGO Recommendations for the Diagnosis and Treatment of Patients with Locally Advanced and Metastatic Breast Cancer: Update 2023.

The Breast Committee of the Arbeitsgemeinschaft Gynäkologische Onkologie (German Gynecological Oncology Group, AGO) presents the 2023 update of the evidence-based recommendations for the diagnosis and treatment of patients with locally advanced and metastatic breast cancer (mBC).

Arbeitsgemeinschaft Gynäkologische Onkologie Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2023.

Background: Each year the interdisciplinary Arbeitsgemeinschaft Gynäkologische Onkologie (AGO), German Gynecological Oncology Group Breast Committee on Diagnosis and Treatment of Breast Cancer provides updated state-of-the-art recommendations for early and metastatic breast cancer. Summary: The updated evidence-based treatment recommendation for early and metastatic breast cancer has been released in March 2023. Key Messages: This paper concisely captures the updated recommendations for early breast cancer chapter by chapter.

[What is confirmed in the prevention, diagnostics and treatment of early breast cancer?] / Was ist gesichert in der Prävention, Diagnostik und Therapie des frühen Mammakarzinoms?

With more than 2.3 million newly diagnosed cases worldwide in 2020, breast cancer is still the most frequent cancer in women and despite improved diagnostics and treatment the most frequent cause of death from cancer. Continuous scientific developments in the areas of prevention, the application of modern diagnostic procedures and treatment options for early breast cancer, have led to an improvement in the 5­year probability of survival. The treatment of early breast cancer is based on a combination of a locoregional and a systemic treatment approach. Depending on the tumor stage and the histological subtype the application of neoadjuvant chemotherapy with or without antibodies or immunotherapy is necessary. This article gives an overview of the current standard in the diagnostics and treatment of early breast cancer, without giving an in-depth elucidation of the differentiated subtype-specific systemic treatment. For this, reference should be made to the relevant literature.

Incidence and Resolution of Eribulin-Induced Peripheral Neuropathy (IRENE) in Locally Advanced or Metastatic Breast Cancer: Prospective Cohort Study.

BACKGROUND: Eribulin, a halichondrin-class microtubule dynamics inhibitor, is a preferred treatment option for patients with advanced breast cancer who have been pretreated with an anthracycline and a taxane. Peripheral neuropathy (PN) is a common side effect of chemotherapies for breast cancer and other tumors. The Incidence and Resolution of Eribulin-Induced Peripheral Neuropathy (IRENE) noninterventional postauthorization safety study assessed the incidence and severity of PN in patients with breast cancer treated with eribulin. PATIENTS AND METHODS: IRENE is an ongoing observational, single-arm, prospective, multicenter, cohort study. Adult patients (≥18 years of age) with locally advanced or metastatic breast cancer and disease progression after 1-2 prior chemotherapeutic regimen(s) for advanced disease were treated with eribulin. Patients with eribulin-induced PN (new-onset PN or worsening of preexisting PN) were monitored until death or resolution of PN. Primary endpoints included the incidence, severity, and time to resolution of eribulin-induced PN. Secondary endpoints included time to disease progression and safety. RESULTS: In this interim analysis (data cutoff date: July 1, 2019), 67 (32.4%) patients experienced any grade eribulin-induced PN, and 12 (5.8%) patients experienced grade ≥3 eribulin-induced PN. Median time to resolution of eribulin-induced PN was not reached. Median time to disease progression was 4.6 months (95% CI, 4.0-6.5). Treatment-emergent adverse events (TEAEs) occurred in 195 (93.8%) patients and serious TEAEs occurred in 107 (51.4%) patients. CONCLUSION: The rates of any grade and grade ≥3 eribulin-induced PN observed in this real-world study were consistent with those observed in phase III randomized clinical trials. No new safety findings were observed.

A Case of Ischemic Monomelic Neuropathy following Endovascular Arteriovenous Fistula Creation and Assisted Maturation.

Dialysis access steal syndrome (DASS) is a phenomenon known to occur following creation of an arteriovenous fistula or arteriovenous graft. The clinical presentation of DASS is characterized by symptoms of limb ischemia due to diversion of arterial flow from the distal extremity. Ischemic monomelic neuropathy (IMN) is a rare subtype of DASS classically described as an acute, isolated presentation of peripheral neuropathy following dialysis access creation. Although the underlying pathophysiology is not entirely understood, the clinical manifestation of IMN is often described as severe distal limb pain that progresses to motor and sensory defects. The onset of IMN may occur immediately following dialysis access creation or intervention. Here, we present a case of IMN following assisted maturation of an endovascular fistula.

Chemokine binding to PSGL-1 is controlled by O-glycosylation and tyrosine sulfation.

Protein glycosylation influences cellular recognition and regulates protein interactions, but how glycosylation functions alongside other common posttranslational modifications (PTMs), like tyrosine sulfation (sTyr), is unclear. We produced a library of 53 chemoenzymatically synthesized glycosulfopeptides representing N-terminal domains of human and murine P-selectin glycoprotein ligand-1 (PSGL-1), varying in sTyr and O-glycosylation (structure and site). Using these, we identified key roles of PSGL-1 O-glycosylation and sTyr in controlling interactions with specific chemokines. Results demonstrate that sTyr positively affects CCL19 and CCL21 binding to PSGL-1 N terminus, whereas O-glycan branching and sialylation reduced binding. For murine PSGL-1, interference between PTMs is greater, attributed to proximity between the two PTMs. Using fluorescence polarization, we found sTyr is a positive determinant for some chemokines. We showed that synthetic sulfopeptides are potent in decreasing chemotaxis of human dendritic cells toward CCL19 and CCL21. Our results provide new research avenues into the interplay of PTMs regulating leukocyte/chemokine interactions.