A5024262881- Cancer Immunotherapy and Biomarkers
- Esophageal Cancer Research and Treatment
- Immune cells in cancer
- Immune Cell Function and Interaction
- Cancer, Hypoxia, and Metabolism
- Ferroptosis and cancer prognosis
- Gastric Cancer Management and Outcomes
- Immunotherapy and Immune Responses
- Cancer Cells and Metastasis
- Lung Cancer Diagnosis and Treatment
- Nanoplatforms for cancer theranostics
- Gastrointestinal Tumor Research and Treatment
- Cancer Genomics and Diagnostics
- Appendicitis Diagnosis and Management
- Pancreatic and Hepatic Oncology Research
- CAR-T cell therapy research
- Phagocytosis and Immune Regulation
- Lymphoma Diagnosis and Treatment
- COVID-19 and healthcare impacts
- Cancer, Stress, Anesthesia, and Immune Response
- Hepatocellular Carcinoma Treatment and Prognosis
- Intraperitoneal and Appendiceal Malignancies
- Cancer, Lipids, and Metabolism
- Chemokine receptors and signaling
- Colorectal and Anal Carcinomas
St. James's Hospital
2019-2025
Trinity College Dublin
2019-2025
Dana-Farber Cancer Institute
2023-2025
Harvard University
2023-2024
Universitatea de Medicină, Farmacie, Științe și Tehnologie „George Emil Palade” din Târgu Mureș
2021
Jackson and Tull (United States)
2021
Creative Research Enterprises (United States)
2021
Cancer Institute (WIA)
2021
The tumour microenvironment is of critical importance in cancer development and progression includes the surrounding stromal immune cells, extracellular matrix, milieu metabolites signalling molecules intercellular space. To support sustained mitotic activity cells must reconfigure their metabolic phenotype. Lactate major by-product such alterations consequently, accumulates tumour. actively contributes to evasion, a hallmark cancer, by directly inhibiting cell cytotoxicity proliferation....
Background: The FLOT protocol and the CROSS trimodality regimen represent current standards in management of locally advanced esophageal adenocarcinoma. In absence published Randomised Controlled Trial data, this propensity-matched comparison evaluated tolerance, toxicity, impact on sarcopenia pulmonary physiology, operative complications, oncologic metrics. Methods: Two hundred twenty-two patients, 111 each arm, were included from 2 high-volume centers. Computed tomography-measured...
The FLOT4-AIO trial established the FLOT regimen as a compelling option for gastric, junctional and esophageal adenocarcinoma. Data on with en-bloc transthoracic esophagectomy (TTE) are limited. This study explored operative complications, tolerance, toxicity, physiological impact, oncologic outcomes.An observational cohort consecutive patients at 3 tertiary centers undergoing TTE. Toxicity, complications (per ECCG definitions), tumor regression grade (TRG), recurrences survival were...
Tumour acidosis contributes to cancer progression by inhibiting anti-tumour immunity. However, the effect of on T cell phenotypes in oesophageal adenocarcinoma (OAC) is unknown. Therefore, this study investigated profiles and if immune checkpoint blockade (ICB) could enhance immunity under acidosis. Acidic conditions substantially altered expression OAC patient-derived cells, upregulating TIM-3, LAG-3 CTLA-4. Severe (pH 5.5) significantly decreased percentage central memory CD4+ an that was...
Persisters are a sub-population of tumor cells that survive anti-cancer therapy facilitating recurrence, and have been identified following drug- immune-therapy but generally considered as distinct entities. Drugs immune often kill via apoptosis, therefore, we tested hypothesis both types based on reduced mitochondrial apoptotic sensitivity, which would yield multi-therapy resistance. We observed IPCs acquired sensitivity to multiple drugs radiotherapy. Likewise, DTPs developed radiotherapy,...
Abstract Background: Persisters are a sub-population of tumor cells that survive anti-cancer therapy and thought to be major cause recurrence. have been identified following both drug- immune-therapy but generally considered very distinct entities. The focus this study is examine any similarities/differences between immunotherapy persister (IPCs) drug tolerant (DTPs). Both pharmacological agents immune often kill via apoptosis. Therefore, we investigated if reduced apoptotic sensitivity...
Use of immune checkpoint inhibitors (ICIs) with chemotherapy to enhance responses in oesophageal adenocarcinoma (OAC) is an attractive approach. We identified subpopulations OAC cells expressing inhibitory (IC) ligands (PD-L1, PD-L2 and CD160) receptors (PD-1, TIGIT, TIM-3, LAG-3 A2aR) vitro ex vivo biopsies. Combination regimens FLOT CROSS promote a more immune-resistant phenotype through upregulation IC on vitro. Importantly, this study investigated if cells, enriched for ICs exhibited...
Esophageal adenocarcinoma (EAC) is an aggressive cancer with poor prognosis and incidence increasing rapidly in the Western world. Multi-modal treatment has improved survival outcomes but only for a minority of patients. Currently no markers have been identified to predict response. This study investigated association between clinical pre-treatment levels 54 serum proteins n = 80 patients EAC. Low tumor regression grade (TRG), corresponding favorable response, was linked prolonged overall...
The presence of an immunosuppressive tumour microenvironment in oesophageal adenocarcinoma (OAC) is a major contributor to poor responses. Novel treatment strategies are required supplement current regimens and improve patient survival. This study examined the immunomodulatory effects that radiation therapy chemokine receptor antagonism impose on T cell phenotypes OAC with primary goal identifying potential therapeutic targets combine anti-tumour Compared healthy controls, function was...
In the contemporary era of cancer immunotherapy, an abundance clinical and translational studies have reported radiotherapy (RT) immunotherapies as a viable option for immunomodulation many subtypes, with related trials ongoing. locally advanced disease, chemotherapy or chemoradiotherapy followed by surgical excision tumour remain principal treatment strategy in oesophageal adenocarcinoma (OAC), however, use host immune system to improve anti-tumour immunity is rapidly garnering increased...
Use of immune checkpoint blockade to enhance T cell-mediated immunity within the hostile tumour microenvironment (TME) is an attractive approach in oesophageal adenocarcinoma (OAC). This study explored effects TME, including nutrient deprivation and hypoxia, on (IC) expression cell phenotypes, potential use nivolumab function under such conditions.ICs were upregulated stromal cells PD-L2, CTLA-4 TIGIT. OAC patient-derived PBMCs co-cultured with OE33 LAG-3 downregulated co-stimulatory marker...
Cisplatin (cis-diamminedichloroplatinum) is widely used for the treatment of solid malignancies; however, development chemoresistance hinders success this chemotherapeutic in clinic. This study provides novel insights into molecular and phenotypic changes an isogenic oesophageal adenocarcinoma (OAC) model acquired cisplatin resistance. Key differences that could be targeted to overcome resistance are highlighted. We characterise sensitivity, gene expression, inflammatory protein secretions,...
Background Immune checkpoint inhibitors (ICIs) are being investigated for their role as an adjunct in the multimodal treatment of esophageal adenocarcinoma (EAC). The most effective time to incorporate ICIs remains unknown. Our study profiles systemic anti-tumor immunity perioperatively help inform optimal timing into current standards care EAC patients. Methods Systemic 11 patients was phenotyped immediately prior esophagectomy (POD-0) and post-operatively (POD)-1, 3, 7 week 6. Longitudinal...
Response rates to immune checkpoint blockade (ICB) remain low in oesophageal adenocarcinoma (OAC). Combining ICB with immunostimulatory chemotherapies boost response is an attractive approach for converting 'cold' tumours into 'hot' tumours. This study profiled (IC) expression on circulating and tumour-infiltrating T cells OAC patients correlated these findings clinical characteristics. The effect of first-line chemotherapy regimens (FLOT CROSS) anti-tumour cell immunity was assessed help...
Esophagogastric adenocarcinomas (EAC) are obesity-associated malignancies underpinned by severe immune dysregulation and inflammation. Our previous work indicates that NK cells migrate to EAC omentum, where they undergo phenotypic functional alterations apoptosis. In this study, we investigate whether such erroneous chemotaxis omentum is paralleled compromised cell infiltration of patient tumor examine the role inflammatory chemokine fractalkine in shaping cell-mediated response. data show...
Abstract Chemotherapy upregulates immune checkpoint (IC) expression on the surface of tumour cells and IC-intrinsic signalling confers a survival advantage against chemotherapy in several cancer-types including oesophageal adenocarcinoma (OAC). However, pathways mediating chemotherapy-induced IC upregulation mechanisms employed by ICs to protect OAC remain unknown. Longitudinal profiling revealed that FLOT-induced OE33 was sustained for up 3 weeks post-treatment, returning baseline upon...
Visceral obesity is a key risk factor in the development of oesophagogastric junctional adenocarcinoma (OGJ), predominantly via generation systemic low grade inflammation. Obesity-induced inflammation promotes resistance to current standards care, enhancing tumour cell growth and survival. This study investigates effect visceral adipose tissue secretome from OGJ patients with early versus advanced tumours on T-cell immunity role immune checkpoint blockade anti-tumour immunity.Visceral...
Oesophagogastric adenocarcinomas (OAC) are poor prognosis, obesity-associated cancers which may benefit from natural killer (NK) cell-based immunotherapies. Cellular immunotherapies encounter two key challenges to their success in OAC, namely recruitment extratumoural tissues such as the omentum at expense of tumour and an immunosuppressive microenvironment (TME) can hamper NK cell function. Herein, we examined approaches overcome detrimental impact obesity on cells We have demonstrated that...