ORCID Profile
0000-0002-5619-1913
Current Organisation
Universiteit Antwerpen
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Publisher: Elsevier BV
Date: 2017
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.22489862.V1
Abstract: Supplementary Figure 2: Virus neutralization test with 50% neutralization titers (NT50) defined as the s le dilution (reciprocal titer) conveying 50% neutralization in SARS-CoV-2 (strains 2019-nCoV-Italy-INMI1 and VLD20211207) infected wells.
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.22489847.V1
Abstract: Supplementary Tables S1-S2
Publisher: Wiley
Date: 2019
DOI: 10.1002/CTI2.1094
Publisher: Informa UK Limited
Date: 12-12-2017
Publisher: American Association for Cancer Research (AACR)
Date: 07-2017
DOI: 10.1158/1538-7445.AM2017-3715A
Abstract: Malignant pleural mesothelioma (MPM) is an aggressive cancer with a poor prognosis for which new therapeutic strategies are available. Data derived from a small number of mesothelioma patients suggest that blocking immune checkpoints could offer new treatment opportunities. Gaining more insight in the immunological aspect of the tumor microenvironment (TME) in MPM is essential to develop an effective immunotherapy. In this context, we investigated expression of the immune checkpoint molecules TIM-3, LAG-3, PD-1 and its ligand PD-L1 on cells in human pleural (collected via thoracocentesis, n=6) and ascites (collected via paracentesis, n=5) MPM fluids and identified different subsets of immune cells in the TME using multicolor flow cytometry. Different types of immune cells in the fluids could be detected, with predominant occurrence of CD3+CD4+ T cells, CD64+ macrophages and CD11c+CD303+ dendritic cells (DCs). CD3+CD8+ T cells, CD3-CD56+ natural killer (NK) cells and CD19+ B cells were also present to a lesser extent. While CD4+ and CD8+ T cells and CD64+ macrophages could be detected in all s les, this was not the case for the other cell types. Ascites fluids contained more podoplanin+ (PDPN) tumor cells compared to pleural fluids (average 3.0% vs 0.3%). PD-1+ T cells and NK cells could be detected in all pleural and 80% of the ascites s les. 64% of all s les contained LAG-3-expressing cells, most frequently in pleural fluids. In all s les CD4+ T-cells and NK cells showed TIM-3 expression and in 82% of the s les TIM-3 was also expressed on CD8+ T-cells. In all ascites s les PD-L1 was expressed on DCs, B cells, macrophages and PDPN+ MPM tumor cells. PD-L1 was also expressed on DCs in all pleural s les while in 67%, 83% and 83% of those s les CD19+, CD64+ and PDPN+ cells were PD-L1+, respectively. Based on the mean fluorescence intensity PDPN+ tumor cells showed the highest PD-L1 expression in both fluids. In conclusion, we provide a detailed analysis of a ersity of immune cells present in MPM fluid s les. We are the first to demonstrate TIM-3 and LAG-3 expression in mesothelioma effusions. Statistical analysis is ongoing to investigate whether there are differences between both fluid types and whether there are associations between the cellular composition of the fluids and survival of the patients. The finding of expression of PD-1, PD-L1, TIM-3 and LAG-3 on immune cells in MPM fluids warrants further investigation of the effect of immune checkpoint blockade in MPM, with TIM-3 and LAG-3 as interesting new targets. Citation Format: Elly Marcq, Jorrit De Waele, Jonas van Audenaerde, Eva Lion, Eva Santermans, Niel Hens, Patrick Pauwels, Jan P. van Meerbeeck, Evelien L. Smits. Effusions of mesothelioma patients: What's in it for immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017 2017 Apr 1-5 Washington, DC. Philadelphia (PA): AACR Cancer Res 2017 (13 Suppl):Abstract nr 3715A. doi:10.1158/1538-7445.AM2017-3715A
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.22489862
Abstract: Supplementary Figure 2: Virus neutralization test with 50% neutralization titers (NT50) defined as the s le dilution (reciprocal titer) conveying 50% neutralization in SARS-CoV-2 (strains 2019-nCoV-Italy-INMI1 and VLD20211207) infected wells.
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.22489865
Abstract: Supplementary Figure 1: Correlation betweenSARS-CoV-2 anti-S1 IgG antibody titers and NT50 values against Wuhan and BA.1 Omicron strains post homologous or heterologous booster vaccination in cancer patients and healthy in iduals.
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.C.6533054.V1
Abstract: Purpose: Patients with cancer display reduced humoral responses after double-dose COVID-19 vaccination, whereas their cellular response is more comparable with that in healthy in iduals. Recent studies demonstrated that a third vaccination dose boosts these immune responses, both in healthy people and patients with cancer. Because of the availability of many different COVID-19 vaccines, many people have been boosted with a different vaccine from the one used for double-dose vaccination. Data on such alternative vaccination schedules are scarce. This prospective study compares a third dose of BNT162b2 after double-dose BNT162b2 (homologous) versus ChAdOx1 (heterologous) vaccination in patients with cancer. Experimental Design: A total of 442 subjects (315 patients and 127 healthy) received a third dose of BNT162b2 (230 homologous vs. 212 heterologous). Vaccine-induced adverse events (AE) were captured up to 7 days after vaccination. Humoral immunity was assessed by SARS-CoV-2 anti-S1 IgG antibody levels and SARS-CoV-2 50% neutralization titers (NT50) against Wuhan and BA.1 Omicron strains. Cellular immunity was examined by analyzing CD4 sup + /sup and CD8 sup + /sup T-cell responses against SARS-CoV-2–specific S1 and S2 peptides. Results: Local AEs were more common after heterologous boosting. SARS-CoV-2 anti-S1 IgG antibody levels did not differ significantly between homologous and heterologous boosted subjects [GMT 1,755.90 BAU/mL (95% CI, 1,276.95–2,414.48) vs. 1,495.82 BAU/mL (95% CI, 1,131.48–1,977.46)]. However, homologous-boosted subjects show significantly higher NT50 values against BA.1 Omicron. Subjects receiving heterologous boosting demonstrated increased spike-specific CD8 sup + /sup T cells, including higher IFNγ and TNFα levels. Conclusions: In patients with cancer who received double-dose ChAdOx1, a third heterologous dose of BNT162b2 was able to close the gap in antibody response. /
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.22489859
Abstract: Supplementary Figure 3: Gating strategy for a representative s le
Publisher: Informa UK Limited
Date: 23-03-2023
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.22489853.V1
Abstract: Supplementary Figure 5: Spike-specific CD8+ T cell responses post homologous or heterologous booster vaccination in subcohorts.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 07-05-2021
Abstract: Unbalanced immune responses to pathogens can be life-threatening although the underlying regulatory mechanisms remain unknown. Here, we show a hypoxia-inducible factor 1α-dependent microRNA (miR)-210 up-regulation in monocytes and macrophages upon pathogen interaction. MiR-210 knockout in the hematopoietic lineage or in monocytes/macrophages mitigated the symptoms of endotoxemia, bacteremia, sepsis, and parasitosis, limiting the cytokine storm, organ damage/dysfunction, pathogen spreading, and lethality. Similarly, pharmacologic miR-210 inhibition improved the survival of septic mice. Mechanistically, miR-210 induction in activated macrophages supported a switch toward a proinflammatory state by lessening mitochondria respiration in favor of glycolysis, partly achieved by downmodulating the iron-sulfur cluster assembly enzyme ISCU. In humans, augmented miR-210 levels in circulating monocytes correlated with the incidence of sepsis, while serum levels of monocyte/macrophage-derived miR-210 were associated with sepsis mortality. Together, our data identify miR-210 as a fine-tuning regulator of macrophage metabolism and inflammatory responses, suggesting miR-210-based therapeutic and diagnostic strategies.
Publisher: MDPI AG
Date: 14-01-2021
Abstract: Malignant pleural mesothelioma (MPM) is an aggressive cancer that is causally associated with previous asbestos exposure in most afflicted patients. The prognosis of patients remains dismal, with a median overall survival of only 9–12 months, due to the limited effectiveness of any conventional anti-cancer treatment. New therapeutic strategies are needed to complement the limited armamentarium against MPM. We decided to focus on the combination of different immune checkpoint (IC) blocking antibodies (Abs). Programmed death-1 (PD-1), programmed death ligand-1 (PD-L1), T-cell immunoglobulin mucin-3 (TIM-3), and lymphocyte activation gene-3 (LAG-3) blocking Abs were tested as monotherapies, and as part of a combination strategy with a second IC inhibitor. We investigated their effect in vitro by examining the changes in the immune-related cytokine secretion profile of supernatant collected from treated allogeneic MPM-peripheral blood mononuclear cell (PBMC) co-cultures. Based on our in vitro results of cytokine secretion, and flow cytometry data that showed a significant upregulation of PD-L1 on PBMC after co-culture, we chose to further investigate the combinations of anti PD-L1 + anti TIM-3 versus anti PD-L1 + anti LAG-3 therapies in vivo in the AB1-HA BALB/cJ mesothelioma mouse model. PD-L1 monotherapy, as well as its combination with LAG-3 blockade, resulted in in-vivo delayed tumor growth and significant survival benefit.
Publisher: Informa UK Limited
Date: 28-11-2016
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.22489859.V1
Abstract: Supplementary Figure 3: Gating strategy for a representative s le
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.IJPARA.2017.02.004
Abstract: A more thorough understanding of the immunological interactions between Fasciola spp. and their hosts is required if we are to develop new immunotherapies to control fasciolosis. Deeper knowledge of the antigens that are the target of the acquired immune responses of definitive hosts against both Fasciola hepatica and Fasciola gigantica will potentially identify candidate vaccine antigens. Indonesian Thin Tail sheep express a high level of acquired immunity to infection by F. gigantica within 4weeks of infection and antibodies in Indonesian Thin Tail sera can promote antibody-dependent cell-mediated cytotoxicity against the surface tegument of juvenile F. gigantica in vitro. Given the high protein sequence similarity between F. hepatica and F. gigantica, we hypothesised that antibody from F. gigantica-infected sheep could be used to identify the orthologous proteins in the tegument of F. hepatica. Purified IgG from the sera of F. gigantica-infected Indonesian Thin Tail sheep collected pre-infection and 4weeks p.i. were incubated with live adult F. hepatica ex vivo and the immunosloughate (immunoprecipitate) formed was isolated and analysed via liquid chromatography-electrospray ionisation-tandem mass spectrometry to identify proteins involved in the immune response. A total of 38 proteins were identified at a significantly higher abundance in the immunosloughate using week 4 IgG, including eight predicted membrane proteins, 20 secreted proteins, nine proteins predicted to be associated with either the lysosomes, the cytoplasm or the cytoskeleton and one protein with an unknown cellular localization. Three of the membrane proteins are transporters including a multidrug resistance protein, an amino acid permease and a glucose transporter. Interestingly, a total of 21 of the 38 proteins matched with proteins recently reported to be associated with the proposed small exosome-like extracellular vesicles of adult F. hepatica, suggesting that the Indonesian Thin Tail week 4 IgG is either recognising in idual proteins released from extracellular vesicles or is immunoprecipitating intact exosome-like extracellular vesicles. Five extracellular vesicle membrane proteins were identified including two proteins predicted to be associated with vesicle transport/ exocytosis (VPS4, vacuolar protein sorting-associated protein 4b and the Niemann-Pick C1 protein). RNAseq analysis of the developmental transcription of the 38 immunosloughate proteins showed that the sequences are expressed over a wide abundance range with 21/38 transcripts expressed at a relatively high level from metacercariae to the adult life cycle stage. A notable feature of the immunosloughates was the absence of cytosolic proteins which have been reported to be secreted markers for damage to adult flukes incubated in vitro, suggesting that the proteins observed are not inadvertent contaminants leaking from damaged flukes ex vivo. The identification of tegument protein antigens shared between F. gigantica and F. hepatica is beneficial in terms of the possible development of a dual purpose vaccine effective against both fluke species.
Publisher: Impact Journals, LLC
Date: 25-05-2017
Publisher: MDPI AG
Date: 27-02-2021
Abstract: Cancer arises from mutations accruing within cancer cells, but the tumor microenvironment (TME) is believed to be a major, often neglected, factor involved in therapy resistance and disease progression. Cancer-associated fibroblasts (CAFs) are prominent and key components of the TME in most types of solid tumors. Extensive research over the past decade revealed their ability to modulate cancer metastasis, angiogenesis, tumor mechanics, immunosuppression, and drug access through synthesis and remodeling of the extracellular matrix and production of growth factors. Thus, they are considered to impede the response to current clinical cancer therapies. Therefore, targeting CAFs to counteract these protumorigenic effects, and overcome the resistance to current therapeutic options, is an appealing and emerging strategy. In this review, we discuss how CAFs affect prognosis and response to clinical therapy and provide an overview of novel therapies involving CAF-targeting agents in lung and pancreatic cancer.
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.22489865.V1
Abstract: Supplementary Figure 1: Correlation betweenSARS-CoV-2 anti-S1 IgG antibody titers and NT50 values against Wuhan and BA.1 Omicron strains post homologous or heterologous booster vaccination in cancer patients and healthy in iduals.
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.22489850
Abstract: Supplementary Figure 6: Correlation between CD4+ and CD8+ T cell responses and SARS-CoV-2 binding antibodies post homologous or heterologous booster vaccination in cancer patients.
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.C.6533054
Abstract: Purpose: Patients with cancer display reduced humoral responses after double-dose COVID-19 vaccination, whereas their cellular response is more comparable with that in healthy in iduals. Recent studies demonstrated that a third vaccination dose boosts these immune responses, both in healthy people and patients with cancer. Because of the availability of many different COVID-19 vaccines, many people have been boosted with a different vaccine from the one used for double-dose vaccination. Data on such alternative vaccination schedules are scarce. This prospective study compares a third dose of BNT162b2 after double-dose BNT162b2 (homologous) versus ChAdOx1 (heterologous) vaccination in patients with cancer. Experimental Design: A total of 442 subjects (315 patients and 127 healthy) received a third dose of BNT162b2 (230 homologous vs. 212 heterologous). Vaccine-induced adverse events (AE) were captured up to 7 days after vaccination. Humoral immunity was assessed by SARS-CoV-2 anti-S1 IgG antibody levels and SARS-CoV-2 50% neutralization titers (NT50) against Wuhan and BA.1 Omicron strains. Cellular immunity was examined by analyzing CD4 sup + /sup and CD8 sup + /sup T-cell responses against SARS-CoV-2–specific S1 and S2 peptides. Results: Local AEs were more common after heterologous boosting. SARS-CoV-2 anti-S1 IgG antibody levels did not differ significantly between homologous and heterologous boosted subjects [GMT 1,755.90 BAU/mL (95% CI, 1,276.95–2,414.48) vs. 1,495.82 BAU/mL (95% CI, 1,131.48–1,977.46)]. However, homologous-boosted subjects show significantly higher NT50 values against BA.1 Omicron. Subjects receiving heterologous boosting demonstrated increased spike-specific CD8 sup + /sup T cells, including higher IFNγ and TNFα levels. Conclusions: In patients with cancer who received double-dose ChAdOx1, a third heterologous dose of BNT162b2 was able to close the gap in antibody response. /
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.22489850.V1
Abstract: Supplementary Figure 6: Correlation between CD4+ and CD8+ T cell responses and SARS-CoV-2 binding antibodies post homologous or heterologous booster vaccination in cancer patients.
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.22489853
Abstract: Supplementary Figure 5: Spike-specific CD8+ T cell responses post homologous or heterologous booster vaccination in subcohorts.
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.22489856
Abstract: Supplementary Figure 4: Spike-specific CD4+ T cell responses post homologous or heterologous booster vaccination in subcohorts.
Publisher: MDPI AG
Date: 16-06-2020
DOI: 10.3390/CELLS9061474
Abstract: The concept of immunogenic cell death (ICD) has emerged as a cornerstone of therapy-induced anti-tumor immunity. To this end, the following chemotherapies were evaluated for their ability to induce ICD in non-small cell lung cancer (NSCLC) cell lines: docetaxel, carboplatin, cisplatin, oxaliplatin and mafosfamide. The ICD hallmarks ATP, ecto-calreticulin, HMGB1, phagocytosis and maturation status of dendritic cells (DCs) were assessed in vitro. Furthermore, an in vivo vaccination assay on C57BL/6J mice was performed to validate our in vitro results. Docetaxel and the combination of docetaxel with carboplatin or cisplatin demonstrated the highest levels of ATP, ecto-calreticulin and HMGB1 in three out of four NSCLC cell lines. In addition, these regimens resulted in phagocytosis of treated NSCLC cells and maturation of DCs. Along similar lines, all mice vaccinated with NSCLC cells treated with docetaxel and cisplatin remained tumor-free after challenge. However, this was not the case for docetaxel, despite its induction of the ICD-related molecules in vitro, as it failed to reject tumor growth at the challenge site in 60% of the mice. Moreover, our in vitro and in vivo data show the inability of oxaliplatin to induce ICD in NSCLC cells. Overall with this study we demonstrate that clinically relevant chemotherapeutic regimens in NSCLC patients have the ability to induce ICD.
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.22489847
Abstract: Supplementary Tables S1-S2
Publisher: Wiley
Date: 31-10-2016
Publisher: MDPI AG
Date: 19-10-2019
Abstract: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers with a low response to treatment and a five-year survival rate below 5%. The ineffectiveness of treatment is partly because of an immunosuppressive tumor microenvironment, which comprises tumor-supportive pancreatic stellate cells (PSCs). Therefore, new therapeutic strategies are needed to tackle both the immunosuppressive PSC and pancreatic cancer cells (PCCs). Recently, physical cold atmospheric plasma consisting of reactive oxygen and nitrogen species has emerged as a novel treatment option for cancer. In this study, we investigated the cytotoxicity of plasma-treated phosphate-buffered saline (pPBS) using three PSC lines and four PCC lines and examined the immunogenicity of the induced cell death. We observed a decrease in the viability of PSC and PCC after pPBS treatment, with a higher efficacy in the latter. Two PCC lines expressed and released damage-associated molecular patterns characteristic of the induction of immunogenic cell death (ICD). In addition, pPBS-treated PCC were highly phagocytosed by dendritic cells (DCs), resulting in the maturation of DC. This indicates the high potential of pPBS to trigger ICD. In contrast, pPBS induced no ICD in PSC. In general, pPBS treatment of PCCs and PSCs created a more immunostimulatory secretion profile (higher TNF-α and IFN-γ, lower TGF-β) in coculture with DC. Altogether, these data show that plasma treatment via pPBS has the potential to induce ICD in PCCs and to reduce the immunosuppressive tumor microenvironment created by PSCs. Therefore, these data provide a strong experimental basis for further in vivo validation, which might potentially open the way for more successful combination strategies with immunotherapy for PDAC.
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.22489856.V1
Abstract: Supplementary Figure 4: Spike-specific CD4+ T cell responses post homologous or heterologous booster vaccination in subcohorts.
Publisher: Elsevier BV
Date: 11-2021
Publisher: American Association for Cancer Research (AACR)
Date: 03-11-2022
DOI: 10.1158/1078-0432.CCR-22-2185
Abstract: Patients with cancer display reduced humoral responses after double-dose COVID-19 vaccination, whereas their cellular response is more comparable with that in healthy in iduals. Recent studies demonstrated that a third vaccination dose boosts these immune responses, both in healthy people and patients with cancer. Because of the availability of many different COVID-19 vaccines, many people have been boosted with a different vaccine from the one used for double-dose vaccination. Data on such alternative vaccination schedules are scarce. This prospective study compares a third dose of BNT162b2 after double-dose BNT162b2 (homologous) versus ChAdOx1 (heterologous) vaccination in patients with cancer. A total of 442 subjects (315 patients and 127 healthy) received a third dose of BNT162b2 (230 homologous vs. 212 heterologous). Vaccine-induced adverse events (AE) were captured up to 7 days after vaccination. Humoral immunity was assessed by SARS-CoV-2 anti-S1 IgG antibody levels and SARS-CoV-2 50% neutralization titers (NT50) against Wuhan and BA.1 Omicron strains. Cellular immunity was examined by analyzing CD4+ and CD8+ T-cell responses against SARS-CoV-2–specific S1 and S2 peptides. Local AEs were more common after heterologous boosting. SARS-CoV-2 anti-S1 IgG antibody levels did not differ significantly between homologous and heterologous boosted subjects [GMT 1,755.90 BAU/mL (95% CI, 1,276.95–2,414.48) vs. 1,495.82 BAU/mL (95% CI, 1,131.48–1,977.46)]. However, homologous-boosted subjects show significantly higher NT50 values against BA.1 Omicron. Subjects receiving heterologous boosting demonstrated increased spike-specific CD8+ T cells, including higher IFNγ and TNFα levels. In patients with cancer who received double-dose ChAdOx1, a third heterologous dose of BNT162b2 was able to close the gap in antibody response.
Publisher: Wiley
Date: 2020
DOI: 10.1002/CTI2.1165
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.PHARMTHERA.2018.04.003
Abstract: Pancreatic cancer is among the three deadliest cancers worldwide with the lowest 5-year survival of all cancers. Despite all efforts, therapeutic improvements have barely been made over the last decade. Even recent highly promising targeted and immunotherapeutic approaches did not live up to their expectations. Therefore, other horizons have to be explored. Natural Killer (NK) cells are gaining more and more interest as a highly attractive target for cancer immunotherapies, both as pharmaceutical target and for cell therapies. In this systematic review we summarise the pathophysiological adaptions of NK cells in pancreatic cancer and highlight possible (future) therapeutic NK cell-related targets. Furthermore, an extensive overview of recent therapeutic approaches with an effect on NK cells is given, including cytokine-based, viro- and bacteriotherapy and cell therapy. We also discuss ongoing clinical trials that might influence NK cells. In conclusion, although several issues regarding NK cells in pancreatic cancer remain unsolved and need further investigation, extensive evidence is already provided that support NK cell oriented approaches in pancreatic cancer.
Publisher: Impact Journals, LLC
Date: 21-09-2017
Location: Belgium
No related grants have been discovered for Jonas Van Audenaerde.