Lavinia Spain
A5010549911- Cancer Genomics and Diagnostics
- Cancer Immunotherapy and Biomarkers
- Melanoma and MAPK Pathways
- Cutaneous Melanoma Detection and Management
- Prostate Cancer Treatment and Research
- CAR-T cell therapy research
- Renal cell carcinoma treatment
- Radiopharmaceutical Chemistry and Applications
- Computational Drug Discovery Methods
- Colorectal Cancer Treatments and Studies
- Brain Metastases and Treatment
- Immunotherapy and Immune Responses
- Renal and related cancers
- Glioma Diagnosis and Treatment
- Cancer, Lipids, and Metabolism
- Molecular Biology Techniques and Applications
- vaccines and immunoinformatics approaches
- Pancreatic and Hepatic Oncology Research
- Cell Image Analysis Techniques
- Microscopic Colitis
- Multiple Myeloma Research and Treatments
- Cancer Diagnosis and Treatment
- Cancer, Stress, Anesthesia, and Immune Response
- Neuroblastoma Research and Treatments
- Immune Cell Function and Interaction
The Francis Crick Institute
2019-2025
Royal Marsden NHS Foundation Trust
2015-2025
Eastern Health
2019-2024
Monash University
2019-2024
Peter MacCallum Cancer Centre
2020-2024
Institute for Biomedicine
2012-2024
UNICEF East Asia and Pacific Regional Office
2018-2024
Continental (Germany)
2012-2024
The University of Melbourne
2023-2024
Royal Marsden Hospital
2015-2020
Clear-cell renal cell carcinoma (ccRCC) exhibits a broad range of metastatic phenotypes that have not been systematically studied to date. Here, we analyzed 575 primary and 335 biopsies across 100 patients with ccRCC, including two cases sampledat post-mortem. Metastatic competence was afforded by chromosome complexity, identify 9p loss as highly selected event driving metastasis ccRCC-related mortality (p = 0.0014). Distinct patterns dissemination were observed, rapid progression multiple...
The evolutionary features of clear-cell renal cell carcinoma (ccRCC) have not been systematically studied to date. We analyzed 1,206 primary tumor regions from 101 patients recruited into the multi-center prospective study, TRACERx Renal. observe up 30 driver events per and show that subclonal diversification is associated with known prognostic parameters. By resolving patterns event ordering, co-occurrence, mutual exclusivity at clone level, we deterministic nature clonal evolution. ccRCC...
Highlights•Anti-CTLA-4 of hIgG1 and hIgG2 isotypes promote depletion intra-tumoral Treg cells•hIgG2 antibodies mediate in vivo cells via CD32a•Anti-CTLA-4 with enhanced Fc effector function improves therapeutic outcomes•The CD16-V158F SNP is associated response to ipilimumab inflamed tumorsSummaryWith the use a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that equivalent tremelimumab regulatory T (Treg) cell vivo, increasing CD8+ ratio promoting tumor rejection....
Clear cell renal carcinoma (ccRCC) is characterized by near-universal loss of the short arm chromosome 3, deleting several tumor suppressor genes. We analyzed whole genomes from 95 biopsies across 33 patients with clear carcinoma. find hotspots point mutations in 5′ UTR TERT, targeting a MYC-MAX-MAD1 repressor associated telomere lengthening. The most common structural abnormality generates simultaneous 3p and 5q gain (36% patients), typically through chromothripsis. This event occurs...
CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that expression largely restricted to tumor-infiltrating Treg in mice humans. While existing were observed deplete the periphery, upregulation of inhibitory Fc gamma receptor (FcγR) IIb tumor site prevented intra-tumoral cell depletion, which may underlie lack...
Treatment with programmed death receptor-1 (PD-1) antibodies is associated high response rates in patients advanced melanoma. Reliable markers for early and outcome are still sparse. We evaluated 66 consecutive advanced/metastatic melanoma treated nivolumab or pembrolizumab between 2013 2014. The main objectives of this study were to investigate whether, first, serum lactate dehydrogenase (LDH) at baseline (normal vs above the upper limit normal) correlates overall survival (OS), and,...
Checkpoint inhibitors are emerging as important cancer therapies but associated with a high rate of immune side effects, including endocrinopathy.To determine the burden thyroid dysfunction in patients melanoma treated checkpoint and describe clinical course.Consecutive either ipilimumab, nivolumab, pembrolizumab or combination ipilimumab nivolumab were identified. Baseline function tests used to exclude those pre-existing abnormalities, during treatment identify dysfunction.Rates overt...
Genetic intra-tumour heterogeneity fuels clonal evolution, but our understanding of clinically relevant dynamics remain limited. We investigated spatial and temporal features diversification in clear cell renal carcinoma through a combination modelling real tumour analysis. observe that the mode growth, surface or volume, impacts extent subclonal diversification, enabling interpretation diversity patient tumours. Specific patterns proliferation necrosis explain expansion emergence parallel...
Abstract Understanding the evolutionary pathways to metastasis and resistance immune-checkpoint inhibitors (ICI) in melanoma is critical for improving outcomes. Here, we present most comprehensive intrapatient metastatic dataset assembled date as part of Posthumous Evaluation Advanced Cancer Environment (PEACE) research autopsy program, including 222 exome sequencing, 493 panel-sequenced, 161 RNA 22 single-cell whole-genome sequencing samples from 14 ICI-treated patients. We observed...
5017 Background: The VISION and TheraP trials have established the safety efficacy of 177 Lu-PSMA-617 in mCRPC with a 50% PSA response rate (PSA50-RR) 46% 66% median progression free survival (PFS) 8.7 5.1 months, respectively. More effective treatments are required as disease remains universal. Immunotherapy has limited single-agent mCRPC. We hypothesise that by potentially inducing immunogenic cell death, may act synergistically pembrolizumab, an anti-programmed death 1 inhibitor, to...
AimImmune checkpoint inhibitor-induced encephalitis (ICI-iE) is a rare but life-threatening toxicity of immune inhibitor treatment. We aim to identify the characteristics ICI-iE and describe factors that discriminate it from herpes simplex virus (HSV)-1 anti-leucine-rich glioma-inactivated 1 (anti-LGI1) encephalitis, as two alternative entities encephalitis.MethodsIn this retrospective multicentre cohort study, we collected patients with reported Side Effect Registry Immuno-Oncology January...