Simone C. Stone
A5077515719- Cancer Immunotherapy and Biomarkers
- Genetic factors in colorectal cancer
- Childhood Cancer Survivors' Quality of Life
- CAR-T cell therapy research
- Cancer Genomics and Diagnostics
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Health Systems, Economic Evaluations, Quality of Life
- Glioma Diagnosis and Treatment
- Neuroblastoma Research and Treatments
- Acute Lymphoblastic Leukemia research
- Single-cell and spatial transcriptomics
- Lung Cancer Treatments and Mutations
- Cervical Cancer and HPV Research
- Colorectal Cancer Treatments and Studies
- Pancreatic and Hepatic Oncology Research
- Immune cells in cancer
- Cancer, Hypoxia, and Metabolism
- Cancer-related Molecular Pathways
- PARP inhibition in cancer therapy
- DNA Repair Mechanisms
- Multiple and Secondary Primary Cancers
- Immune Response and Inflammation
- Cytokine Signaling Pathways and Interactions
University of Toronto
2023-2025
Princess Margaret Cancer Centre
2018-2023
University Health Network
2018-2023
Universidade de São Paulo
2013-2020
Centro Regional de Derechos Humanos y Justicia de Género, Corporación Humanas
2017
Universidade Federal de Pelotas
2012
Abstract Cancers arising from germline DNA mismatch repair deficiency or polymerase proofreading (MMRD and PPD) in children harbour the highest mutational microsatellite insertion–deletion (MS-indel) burden humans. MMRD PPD cancers are commonly lethal due to inherent resistance chemo-irradiation. Although immune checkpoint inhibitors (ICIs) have failed benefit previous studies, we hypothesized that hypermutation caused by will improve outcomes following ICI treatment these patients. Using an...
Regulatory T (Treg) cells expressing the transcription factor FOXP3 are essential for maintenance of immunologic self-tolerance but play a detrimental role in most cancers due to their ability suppress antitumor immunity. The phenotype human circulating Treg has been extensively studied, less is known about tumor-infiltrating cells. We studied and function ovarian cancer melanoma identify potential cell-associated molecules that can be targeted by tumor immunotherapies.
Checkpoint inhibitors have limited efficacy for children with unselected solid and brain tumors. We report the first prospective pediatric trial (NCT02992964) using nivolumab exclusively refractory nonhematologic cancers harboring tumor mutation burden (TMB) ≥5 mutations/megabase (mut/Mb) and/or mismatch repair deficiency (MMRD).
Cervical cancer continues to be a public health problem in developing countries. Previous studies have shown that cervical cells display markers of aerobic glycolysis, indicating these tumors are likely secrete lactate. Mostly, lactate is recognized as molecule capable suppressing immune responses, through inhibition T cells, Mϕs, and dendritic cells. We others previously Mϕs frequent infiltrating cancers with the ability inhibit antitumor responses promote tumor growth angiogenesis. Here,...
Human papillomavirus (HPV) is the main etiological factor for cervical cancer development. HPV also associated with other anogenital and oropharyngeal tumors. tumors are frequent constitute a public health problem, mainly in developing countries. Therapy against such usually excisional, causing iatrogenic morbidity. Therefore, development of strategies new therapies desirable. The tumor microenvironment essential growth, where inflammation an important component, displaying central role...
The RAS/MAPK pathway is an emerging targeted across a spectrum of both adult and pediatric cancers. Typically, this associated with single, well-characterized point mutation in oncogene. Hypermutant tumors that harbor many somatic mutations may obscure the interpretation such targetable genomic events. We find replication repair-deficient (RRD) cancers, which are universally hypermutant affect children born RRD cancer predisposition, enriched for (P = 10-8). These not random, exist...
Background: HCC is the most common form of primary liver cancer and 3rd leading cause death globally. Combination atezolizumab-bevacizumab (AB) demonstrated an impressive 19-month median survival in 1st line (IMbrave-150) a HR (0.66) that has not been surpassed by newer combinations remains important standard care with ORR 32%. Despite advancements treatment advanced HCC, ∼30% patients demonstrate no response to therapy. It theorized there dynamic interplay between TIME HCC. We performed...
Tumors are complex structures containing different types of cells and molecules. The importance the tumor microenvironment in progression, growth, maintenance is well-established. However, effects not restricted to microenvironment. Molecules secreted by, as well that migrate from tumors, may circulate reach other tissues. This cause a series systemic effects, including modulation immune responses, some cases, leukocytosis metastasis promotion. Leukocytosis has been described poor prognostic...
Platelet-activating factor (PAF) plays an important role in the pathogenesis of several types tumors. The biological effects PAF are mediated by receptor (PAFR), which can be expressed tumor cells and host that infiltrate microenvironment. In present study, we investigated PAFR leukocytes two tumors, one expresses (TC-1 carcinoma) another does not express (B16F10 melanoma) implanted mice or (PAFR KO). It was found both tumors grew significantly less KO than wild-type (WT) mice. Analysis...
Cervical cancer, which main etiologic factor is Human Papillomavirus (HPV) infection, continues to be a burden for public health systems in developing countries. Our laboratory has been working with the hypothesis that signals generated tumor microenvironment can modulate local and systemic immune responses. In this context, it would reasonable think tumors create pro-tumoral bias cells, even before they are recruited microenvironment. To understand if how signaling started influence cells...
<div>AbstractPurpose:<p>Checkpoint inhibitors have limited efficacy for children with unselected solid and brain tumors. We report the first prospective pediatric trial (NCT02992964) using nivolumab exclusively refractory nonhematologic cancers harboring tumor mutation burden (TMB) ≥5 mutations/megabase (mut/Mb) and/or mismatch repair deficiency (MMRD).</p>Patients Methods:<p>Twenty patients were screened, 10 ultimately included in response cohort of whom nine had TMB...
<p>Pathological complete remission in metastatic colorectal adenocarcinoma. (A) Baseline (hematoxylin-eosin, CD8 and PD-L1). (B) Post-nivolumab: no detectable tumor cells, increased inflammation, increase PD-L1 expression. All IHC images are 100X.</p>
<p>Results of time-dependent co-variate and landmark analyses at time-points 3 6 months the trial</p>
<div>Abstract<p>Purpose: Checkpoint-inhibitors have limited efficacy for children with unselected solid and brain tumors. We report the first prospective pediatric trial (NCT02992964) using nivolumab exclusively refractory non-hematological cancers harboring tumor mutation burden (TMB) ≥5 mutations/megabase (mut/Mb) and/or mismatch-repair deficiency (MMRD). Patients methods: Twenty patients were screened, ten ultimately included in response cohort of whom nine had TMB...
<p>Pathological complete remission in metastatic colorectal adenocarcinoma. (A) Baseline (hematoxylin-eosin, CD8 and PD-L1). (B) Post-nivolumab: no detectable tumor cells, increased inflammation, increase PD-L1 expression. All IHC images are 100X.</p>
<p>Full trial protocol NCT02992964</p>
<p>Full trial protocol NCT02992964</p>
<p>Results of time-dependent co-variate and landmark analyses at time-points 3 6 months the trial</p>
Abstract Cancers arising from germline DNA mismatch-repair or polymerase-proofreading deficiencies (MMRD and PPD) in children harbour the highest mutational microsatellite insertion/deletion (MS-indel) burden humans are lethal due to inherent resistance chemo-irradiation. Although immune checkpoint inhibitors (ICI) have failed benefit previous studies, we hypothesized that hypermutation caused by MMRD PPD will improve outcomes following ICI these patients. treatment of 45...
Single cell phenotyping using molecular or protein multiplexing techniques is gaining momentum, especially in the characterization of cancer and tumor microenvironment. It has proven to be particularly useful studying extent heterogeneity cancer, profiling immune environment assess whether certain subsets could predictive treatment response. Using a sequential marker labelling system called Multiplex Immunofluorescence (MxIF, GE Research), we have developed quantitative image analysis...