A5083838208- Cancer Genomics and Diagnostics
- Cancer Immunotherapy and Biomarkers
- Endometrial and Cervical Cancer Treatments
- Immunotherapy and Immune Responses
- Reproductive System and Pregnancy
- Ovarian cancer diagnosis and treatment
- Chemokine receptors and signaling
- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- CRISPR and Genetic Engineering
- Virus-based gene therapy research
- Radiopharmaceutical Chemistry and Applications
- Cancer Research and Treatments
- Genetic factors in colorectal cancer
- CAR-T cell therapy research
- Monoclonal and Polyclonal Antibodies Research
- Sarcoma Diagnosis and Treatment
- RNA Research and Splicing
- Click Chemistry and Applications
- Microtubule and mitosis dynamics
- Cancer-related molecular mechanisms research
- Cervical Cancer and HPV Research
- Nanoplatforms for cancer theranostics
- Immune cells in cancer
- Chronic Lymphocytic Leukemia Research
Leiden University Medical Center
2015-2022
Leiden University
2016-2018
Abstract Purpose: Recent studies have shown that 7% to 12% of endometrial cancers are ultramutated due somatic mutation in the proofreading exonuclease domain DNA replicase POLE. Interestingly, these tumors an excellent prognosis. In view emerging data linking burden, immune response, and clinical outcome cancer, we investigated whether POLE-mutant showed evidence increased immunogenicity. Experimental Design: We examined infiltration activation according tumor POLE a molecularly defined...
The chemokine CXCL13 mediates recruitment of B cells to tumors and is essential for the formation tertiary lymphoid structures (TLSs). TLSs are thought support antitumor immunity associated with improved prognosis. However, it remains unknown whether formed in response general inflammatory character tumor microenvironment, or rather, induced by (neo)antigen-specific adaptive immunity. We here report on finding that TGFβ-dependent CD103+CD8+ tumor-infiltrating T-cell (TIL) subpopulation...
High-risk endometrial cancer (EC) is an aggressive disease for which new therapeutic options are needed. Aims of this study were to validate the enhanced immune response in highly mutated ECs and explore profiles other EC subgroups. We evaluated infiltration 116 high-risk from TransPORTEC consortium, previously classified into four molecular subtypes: (i) ultramutated POLE exonuclease domain-mutant (POLE-mutant); (ii) hypermutated microsatellite unstable (MSI); (iii) p53-mutant; (iv) no...
Genomic instability, which is a hallmark of cancer, generally thought to occur in the middle late stages tumourigenesis, following acquisition permissive molecular aberrations such as TP53 mutation or whole genome doubling. Tumours with somatic POLE exonuclease domain mutations are notable for their extreme genomic instability (their burden among highest human cancer), distinct mutational signature, lymphocytic infiltrate, and excellent prognosis. To what extent these characteristics...
Studies in early-stage, predominantly low- and intermediate-risk endometrial cancer have demonstrated that L1 cell adhesion molecule (L1CAM) overexpression identifies patients at increased risk of recurrence, yet its prognostic significance high-risk is unclear. To evaluate this, frequency, the relationship L1CAM with established biomarker p53, we analyzed expression both markers by immunohistochemistry a pilot series 116 cancers (86 endometrioid, 30 non-endometrioid subtype) features (such...
Abstract Purpose: Pathogenic POLE proofreading domain mutations are found in many malignancies where they associated with ultramutation and favorable prognosis. The extent to which this prognosis depends on their sensitivity adjuvant treatment is unknown, as the optimal therapy for advanced-staged or recurrent POLE-mutant cancers. Experimental Design: We examined recurrence-free survival of women POLE–wild-type endometrial cancers (EC) observation arm randomized PORTEC-1 cancer trial (N =...
Aims POLE exonuclease domain mutations identify a subset of endometrial cancer ( EC ) patients with an excellent prognosis. The use this biomarker has been suggested to refine adjuvant treatment decisions, but the necessary sequencing is not widely performed and relatively expensive. Therefore, we aimed histopathological immunohistochemical characteristics aid in detection ‐ mutant s. Methods results Fifty‐one endometrioid, 67 wild‐type endometrioid 15 serous s were included (total N = 133)....
Endometrial cancers (ECs) with POLE proofreading mutations are typified by ultramutation and excellent prognosis. We investigated whether these were related, found that POLE-mutant ECs display a robust T cell response corresponds to an enrichment of antigenic tumor neopeptides. Enhanced immunogenicity may explain the favorable outcome ECs.
// Manouk van Esterik 1 , Inge C. Van Gool Cor D. de Kroon 2 Remi A. Nout 3 Carien L. Creutzberg Vincent T.H.B.M. Smit Tjalling Bosse Ellen Stelloo Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands Gynaecology, Radiation Oncology, Correspondence to: Bosse, email: T.Bosse@lumc.nl Keywords: endometrial cancer, intratumour heterogeneity, molecular markers, prognostic, risk stratification Received: December 16, 2016 Accepted: February 07, 2017 Published: March...
<p>Supplementary figure 2. CD3+ tumor infiltrate according to EC molecular subtype</p>
<p>Supplementary figure 4. CD20+ and FOXP3+ tumor infiltrate according to EC molecular subtype</p>
<p>Supplementary figure 3. Number of TIA-1+ cytolytic T cells according to molecular subtype</p>
<p>Supplementary figure 1. Tumor infiltrating lymphocytes and Crohn's like reaction in POLE- mutant endometrioid endometrial cancers</p>
<p>Supplementary figure 5. Expression of T cell markers and cytotoxic effectors by EC molecular subtype</p>
<p>Supplementary figure 6. T cell exhaustion markers according to tumor CD8A expression and EC molecular subtype</p>