A5073909290- Immune cells in cancer
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Cancer Research and Treatments
- Cancer, Hypoxia, and Metabolism
- Virus-based gene therapy research
- Anesthesia and Pain Management
- Cancer Diagnosis and Treatment
- Epilepsy research and treatment
- Advances in Oncology and Radiotherapy
- Genomics, phytochemicals, and oxidative stress
- Hepatitis B Virus Studies
- Metabolism and Genetic Disorders
- Acute Myeloid Leukemia Research
- Cytomegalovirus and herpesvirus research
- Immunotherapy and Immune Responses
- Lung Cancer Diagnosis and Treatment
- Viral Infections and Outbreaks Research
- Autophagy in Disease and Therapy
- Nausea and vomiting management
- Chemokine receptors and signaling
- Histone Deacetylase Inhibitors Research
- Viral Infections and Vectors
- Hematopoietic Stem Cell Transplantation
The University of Texas MD Anderson Cancer Center
2024-2025
European Institute of Oncology
2020-2025
Istituti di Ricovero e Cura a Carattere Scientifico
2023-2024
University of Parma
2016
CD8+ T cells are master effectors of antitumor immunity, and their presence at tumor sites correlates with favorable outcomes. However, metabolic constraints imposed by the microenvironment (TME) can dampen ability to control progression. We describe lipid accumulation in TME areas pancreatic ductal adenocarcinoma (PDA) populated infiltrating both murine human tumors. In this lipid-rich but otherwise nutrient-poor TME, access using metabolism becomes particularly valuable for sustaining cell...
The metabolic state represents a major hurdle for an effective adoptive T cell therapy (ACT). Indeed, specific lipids can harm CD8+ (CTL) mitochondrial integrity, leading to defective antitumor responses. However, the extent which affect CTL functions and fate remains unexplored. Here, we show that linoleic acid (LA) is positive regulator of activity by improving fitness, preventing exhaustion, stimulating memory-like phenotype with superior effector functions. We report LA treatment...
CD8+ T cells are a major prognostic determinant in solid tumors, including colorectal cancer (CRC). However, understanding how the interplay between different immune impacts on clinical outcome is still its infancy. Here, we describe that interaction of tumor infiltrating neutrophils expressing high levels CD15 with effector memory (TEM) correlates progression. Mechanistically, stromal cell-derived factor-1 (CXCL12/SDF-1) promotes retention within increasing crosstalk cells. As consequence...
Myelodysplastic syndrome and acute myeloid leukemia (AML) belong to a continuous disease spectrum of malignancies with poor prognosis in the relapsed/refractory setting necessitating novel therapies. Natural killer (NK) cells from patients display global dysfunction impaired killing capacity, altered metabolism, an exhausted phenotype at single-cell transcriptomic proteomic levels. In this study, we identified that was mediated through cross-talk between NK blasts cell-cell contact. cell...
Abstract NK cells represent key players capable of driving antitumor immune responses. However, the potent immunosuppressive activity tumor microenvironment (TME) may impair their effector function. Here, we strengthen importance metabolic interactions between and TME propose dysfunction as one major mechanisms behind failure in cancer treatment. In particular, described that has a direct negative impact on cell function by disrupting mitochondrial integrity pediatric adult patients with...
The lysine-specific histone demethylase 1 A (LSD1) is involved in antitumor immunity; however, its role shaping CD8 + T cell (CTL) differentiation and function remains largely unexplored. Here, we show that pharmacological inhibition of LSD1 (LSD1i) CTL the context adoptive therapy (ACT) elicits phenotypic functional alterations, resulting a robust immunity preclinical models female mice. In addition, combination anti-PDL1 treatment with LSD1i-based ACT eradicates tumor leads to long-lasting...
ABSTRACT Accumulation of lipids in the tumor microenvironment (TME) is a feature several solid tumors and increased palmitate (PA) availability fosters progression metastases. The intrinsic effects PA on cancer cells are well understood, but its role modulating CD8 + T (CTL) functional performances remains elusive. Here, we found that alters mitochondrial metabolism CTL prevents their effector functions an irreversible manner, resulting impaired antitumoral immunity. Mechanistically,...
Abstract Adoptive cell therapy using engineered natural killer (NK) cells has emerged as a promising new treatment, with gene editing offering opportunities to further increase antitumor potency. However, strategies address both intrinsic and extrinsic therapeutic barriers remain largely unexplored. To this, we developed pooled CRISPR discovery platform identify genetic perturbations that can be exploited for CAR-NK cellular engineering strategies. Using primary human NK cells, performed...
Abstract Chimeric antigen receptor (CAR) natural killer (NK) cell immunotherapy offers a promising approach against cancer. However, the molecular mechanisms governing CAR NK activity remain poorly understood. In this study, we identified transcription factor cAMP response element modulator (CREM) as pivotal regulator of function. Using Raji model, single-cell RNA sequencing revealed marked upregulation CREM in cells during peak anti-tumor after adoptive transfer. expression correlated with...
Ebola virus (EBOV) is a Category A pathogen that member of Filoviridae family causes hemorrhagic fever in humans and non-human primates. Unpredictable devastating outbreaks disease have recently occurred Africa current immunoprophylaxis therapies are limited. The main limitation working with pathogens like EBOV the need for costly containment. To potentiate further wider opportunity prophylactics development, innovative approaches necessary. In present study, an antigen delivery platform...
<h3>Background</h3> Adoptive cell therapy (ACT) harnesses the immune system to recognise tumor cells and carry out an anti-tumor function. However, metabolic constraints imposed by tumour microenvironment (TME) suppress responses of CTL reshaping their metabolism epigenetic landscape. We have recently demonstrated that progressive accumulation specific long-chain fatty acids (LCFAs) impair mitochondrial function drives CD8+ T dysfunction. In this scenario, maintaining in a...
ABSTRACT The lysine-specific histone demethylase 1A (LSD1) has been described to play a role in antitumor immunity; however, the of LSD1 shaping CD8+ T cell (CTL) differentiation and function is not understood. Here, we showed that pharmacological inhibition (LSD1i) CTL elicited phenotypic functional alterations led robust immunity context adoptive therapy (ACT). In addition, combination anti-PDL1 with LSD1i-based ACT resulted complete tumor eradication long-lasting tumor-free survival. This...
Abstract Background. A comprehensive understanding of the role immune reactions in progression early-stage colorectal cancer (CRC) is currently lacking. Tumor infiltration by cytotoxic CD8+ T cells has been associated with a better prognosis several solid tumors, including CRC, and high levels memory prevent early metastatic invasion are survival. However, tumor infiltrate highly heterogeneous and, although influence various myeloid cell populations on activity reported, our interplay...
ABSTRACT Tumor contexture has emerged as a major prognostic determinant and tumor infiltrating CD8 + T cells have been associated with better prognosis in several solid tumors, including early-stage colorectal cancer (CRC). However, the immune infiltrate is highly heterogeneous understanding how interplay between different cell compartments impacts on clinical outcome still its infancy. Here, we describe prospective cohort novel effector memory population, which characterized by high levels...