A5087019873- Immune cells in cancer
- Immune Cell Function and Interaction
- Cancer, Hypoxia, and Metabolism
- Cancer Immunotherapy and Biomarkers
- Single-cell and spatial transcriptomics
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Chemokine receptors and signaling
- T-cell and B-cell Immunology
- Cell Adhesion Molecules Research
- Advanced Biosensing Techniques and Applications
- Gene expression and cancer classification
- Histiocytic Disorders and Treatments
- S100 Proteins and Annexins
- Ferroptosis and cancer prognosis
- Lymphatic System and Diseases
- Immune Response and Inflammation
- Neuroinflammation and Neurodegeneration Mechanisms
- Real-time simulation and control systems
- Mast cells and histamine
- Systemic Sclerosis and Related Diseases
- Monoclonal and Polyclonal Antibodies Research
- Epigenetics and DNA Methylation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Lymphatic Disorders and Treatments
Dartmouth College
2017-2022
Dartmouth Cancer Center
2022
King's College London
2009-2017
Guy's Hospital
2017
Most tissues develop from stem cells and precursors that undergo differentiation as their proliferative potential decreases. Mature differentiated rarely proliferate are replaced at the end of life by new derived precursors. Langerhans (LCs) epidermis, although myeloid origin, were shown to renew in independently bone marrow, suggesting existence a dermal or epidermal progenitor. We investigated mechanisms involved LC development homeostasis. observed single wave was recruited epidermis mice...
Tumor hypoxia is a negative prognostic factor that implicated in oncogenic signal activation, immune escape, and resistance to treatment. Identifying the mechanistic role of escape immune-checkpoint inhibitors may aid identification therapeutic targets. We others have shown V-domain Ig suppressor T-cell activation (VISTA), checkpoint regulator B7 family, highly expressed tumor microenvironment models primary human cancers. In this study, we show VISTA HIF1α activity are correlated cohort...
Langerhans cell histiocytosis (LCH) features inflammatory granuloma characterised by the presence of CD1a+ dendritic cells or 'LCH cells'. Badalian-Very et al. recently reported a canonical (V600E)B-RAF mutation in 57% paraffin-embedded biopsies from LCH granuloma. Here we confirm their findings and report identification two novel B-RAF mutations detected patients.Mutations were observed samples 11 out 16 patients using 'next generation' pyrosequencing. In 9 cases identified was...
CD4+ T cells differentiate into phenotypically distinct helper upon antigenic stimulation. Regulation of plasticity between these T-cell lineages is critical for immune homeostasis and prevention autoimmune disease. However, the factors that regulate lineage stability are largely unknown. Here we investigate a role retinoic acid (RA) in regulation using 1 (Th1) cells, traditionally considered most stable Th subset. We found RA, through its receptor RARα, sustains expression Th1 specifying...
The role of negative checkpoint regulators (NCRs) in human health and disease cannot be overstated. V-domain Ig-containing Suppressor T-cell Activation (VISTA) is an Ig superfamily protein predominantly expressed within the hematopoietic compartment has been studied for its regulation T cell responses. findings presented this study show that, unlike all other NCRs, VISTA deficiency dramatically impacts on macrophage cytokine chemokine production, as well chemotactic response VISTA-deficient...
Background: Cardiac transplantation is an excellent treatment for end-stage heart disease. However, rejection of the donor graft, in particular, by chronic leading to cardiac allograft vasculopathy, remains a major cause graft loss. The lymphatic system plays crucial role alloimmune response, facilitating trafficking antigen-presenting cells draining lymph nodes. encounter with T lymphocytes secondary lymphoid organs essential initiation alloimmunity. Donor vessels are not anastomosed that...
Background: Langerhans cell histiocytosis (LCH) features inflammatory granuloma characterised by the presence of CD1a+ dendritic cells or 'LCH cells'.Badalian-Very et al. recently reported a canonical V600E B-RAF mutation in 57% paraffin-embedded biopsies from LCH granuloma.Here we confirm their findings and report identification two novel mutations detected patients.Methods Results: Mutations were observed samples 11 out 16 patients using 'next generation' pyrosequencing.In 9 cases...
Abstract Myeloid derived suppressor cells (MDSC) are elevated in tumors and draining lymph nodes of cancer patients produce a variety immune suppressive factors that impair T cell activation anti-tumor immunity. MDSC also recruited from the bone marrow response to activation, including immunotherapies activate cells. As monocytes significant producers IL6, IL1β TNFα, their elevation can promote pathologic levels these cytokines leading potentially serious conditions such as cytokine release...
<div>Abstract<p>V domain immunoglobulin suppressor of T-cell activation (VISTA) is a premier target for cancer treatment due to its broad expression in many types and enhanced upon development adaptive immune checkpoint resistance. In the CT26 colorectal model, monotherapy small tumors with anti-VISTA resulted slowed tumor growth. combination therapy setting, large showed complete resistance anti–PD-1/CTLA-4, but inclusion led rejection half tumors. Mechanisms antitumor immunity...
<p>Supplementary Figure Legends</p>
<p>Quality control and cluster identification of CD45-enriched scRNAseq data. In the I/V model, BALB/c mice were administered 100k CT26 cells treated when tumors reached a size 40mm3 with isotype (I) or anti-VISTA (V). CPV anti-CTLA-4 anti-PD-1 plus (CP) (CPV) 600mm3. both models, CD45+ isolated from TME analyzed by scRNAseq. (A) Histogram number reads (left) genes (right) detected in all within dataset. (B) CP/CPV (C) Visual representation lymphoid myeloid cell distributions between...
<p>Supplementary Figure S3. Anti-VISTA-induced changes to tumor-infiltrating immune cells in MB49. B6 mice were injected intra-dermally with 100k MB49 and treated when tumors reached a size of 100mm3 isotype (I) or anti-VISTA (V). (A) Macrophage monocyte ratio as determined by flow cytometry (B) (CD45+, CD11b+, Gr1-, F4/80hi) frequency per gram tumor cytometry. Expression iNOS (C), MHC-II (D), CD40 (E), was on CD45+, F4/80+ macrophages (F) expression within granulocytes Ly6G+, F4/80-)...
<p>Additional data supporting Figure 3. (A) Pathway enrichment for each cluster described in figure (B) Comparison of myeloid clusters from this study with those identified by [30]. Dots represent the proportion (bottom) Gubin et al. (left). Each row is normalized sums. Cluster identity [30] was obtained original publication. (C) frequencies as a infiltrate I/V or CP/CPV treatment.</p>
<p>Supplementary Figure S4. Additional data supporting 6. In the I/V model, BALB/c mice were administered 100k CT26 cells and treated when tumors reached a size of 40mm3 with isotype (I) or anti-VISTA (V). CPV anti-CTLA-4 anti-PD-1 plus (CP) (CPV) 600mm3. CD45 + (A-C, E) CD8+ AH1-tetramer+ (D) isolated from TME analyzed by scRNAseq. (A) Stacked bar graph showing all lymphoid cluster frequencies as proportion infiltrate for CP/CPV. (B) NK (C) T cell Mean in CP/CPV treatment. (E) Violin...
<div>Abstract<p>V domain immunoglobulin suppressor of T-cell activation (VISTA) is a premier target for cancer treatment due to its broad expression in many types and enhanced upon development adaptive immune checkpoint resistance. In the CT26 colorectal model, monotherapy small tumors with anti-VISTA resulted slowed tumor growth. combination therapy setting, large showed complete resistance anti–PD-1/CTLA-4, but inclusion led rejection half tumors. Mechanisms antitumor immunity...
<p>Supplementary Figure Legends</p>
<p>Supplementary Figure S4. Additional data supporting 6. In the I/V model, BALB/c mice were administered 100k CT26 cells and treated when tumors reached a size of 40mm3 with isotype (I) or anti-VISTA (V). CPV anti-CTLA-4 anti-PD-1 plus (CP) (CPV) 600mm3. CD45 + (A-C, E) CD8+ AH1-tetramer+ (D) isolated from TME analyzed by scRNAseq. (A) Stacked bar graph showing all lymphoid cluster frequencies as proportion infiltrate for CP/CPV. (B) NK (C) T cell Mean in CP/CPV treatment. (E) Violin...
<p>Quality control and cluster identification of CD45-enriched scRNAseq data. In the I/V model, BALB/c mice were administered 100k CT26 cells treated when tumors reached a size 40mm3 with isotype (I) or anti-VISTA (V). CPV anti-CTLA-4 anti-PD-1 plus (CP) (CPV) 600mm3. both models, CD45+ isolated from TME analyzed by scRNAseq. (A) Histogram number reads (left) genes (right) detected in all within dataset. (B) CP/CPV (C) Visual representation lymphoid myeloid cell distributions between...
<p>Supplementary Figure S3. Anti-VISTA-induced changes to tumor-infiltrating immune cells in MB49. B6 mice were injected intra-dermally with 100k MB49 and treated when tumors reached a size of 100mm3 isotype (I) or anti-VISTA (V). (A) Macrophage monocyte ratio as determined by flow cytometry (B) (CD45+, CD11b+, Gr1-, F4/80hi) frequency per gram tumor cytometry. Expression iNOS (C), MHC-II (D), CD40 (E), was on CD45+, F4/80+ macrophages (F) expression within granulocytes Ly6G+, F4/80-)...
<p>Additional data supporting Figure 3. (A) Pathway enrichment for each cluster described in figure (B) Comparison of myeloid clusters from this study with those identified by [30]. Dots represent the proportion (bottom) Gubin et al. (left). Each row is normalized sums. Cluster identity [30] was obtained original publication. (C) frequencies as a infiltrate I/V or CP/CPV treatment.</p>