A5058976782- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Neuroinflammation and Neurodegeneration Mechanisms
- Single-cell and spatial transcriptomics
- Adenosine and Purinergic Signaling
- Monoclonal and Polyclonal Antibodies Research
- Tryptophan and brain disorders
- Bipolar Disorder and Treatment
- Immune cells in cancer
- RNA Interference and Gene Delivery
Dartmouth College
2020-2025
Dartmouth Cancer Center
2024-2025
Tumor Infiltrating Lymphocyte (TIL) therapy involves the isolation and ex vivo expansion of TIL for treatment solid tumors. The T cell receptor (TCR) repertoires present within drug products (DPs) are highly patient unique include TCRs specific against tumor antigens at variable frequencies. clinical activity is thought to be mediated in part by anti-tumor functionality profile frequency reactive cells (TRTs) DP. Seeking improve therapy, we developed KSQ-001EX KSQ-004EX, two...
The ecto-ATPase CD39 is expressed on exhausted CD8+ T cells in chronic viral infection and has been proposed as a marker of tumor-specific cancer, but the role an effector memory cell response not clearly defined. We report that Ag-specific short-lived cells, while it's co-ectoenzyme, CD73, found precursor (MPECs) vivo. Inhibition enzymatic activity during vitro priming enhances MPEC differentiation vivo after transfer infection. enriched phenotype associated with enhanced tissue resident...
Overcoming immune suppression is a major barrier to eliciting potent CD8
The study of Ag-specific lymphocytes has been a key advancement in immunology over the past few decades. development multimerized probes containing Ags, peptide:MHC complexes, or other ligands was one innovation allowing direct by flow cytometry. Although these types are now common and performed thousands laboratories, quality control assessment probe often minimal. In fact, many made in-house, protocols vary between laboratories. multimers can be obtained from commercial sources core...
The ecto-ATPase CD39 is expressed on exhausted CD8+ T cells in chronic viral infection and has been proposed as a marker of tumor-specific cancer, but the role an effector memory cell response not clearly defined. We report that antigen-specific short-lived (SLECs), while it's co-ecto-enzyme, CD73, found precursor (MPEC)
This pilot study sought to evaluate the circulating levels of immune cells, particularly regulatory T-cell (Treg) subsets, before and after lung resection for non-small cell cancer. Twenty-five patients consented had specimens collected. Initially, peripheral blood 21 was collected studies. Two these were excluded due technical issues, leaving 19 analyses cells. Standard gating high-dimensional unsupervised clustering flow cytometry performed. The blood, tumors lymph nodes analyzed via...
Abstract Resident memory (Trm) cells play an essential role in anti-tumor immunity. However, little is known about the precursors that differentiate into protective Trm populations against cancer. Here we employed established model of B16 melanoma neoadjuvant anti-CD4 therapy, to track tumor antigen-specific CD8+ T through tissues and across time; from their priming as effectors differentiation Trm. We show tumor-draining lymph nodes (TDLNs) contain Teff begin express canonical markers CD103...
Abstract Preclinical and clinical studies have used antibodies to deplete CD4-expressing cells promote anti-tumor immunity. Specifically, a monoclonal anti-CD4 antibody (anti-CD4) has been employed remove FOXP3+ CD4+ regulatory T (Tregs), which are known impede Our previous demonstrated that administering during B16 melanoma tumor growth in mice leads the generation of Ag-specific CD8 disseminate form memory following surgical excision. However, importance co-depleting other cell...
Abstract Resident memory CD8 +(T RM) cells persist in tissues and are critical mediators of the host anti-tumor response. We previously demonstrated that protective, melanoma/melanocyte antigen-specific +T RMcells generated skin B16 tumor-draining lymph nodes (LNs) mice following CD4 cell depletion tumor excision surgery. Whereas TGF-β IL-7 have been shown to play important roles generating viral Ag-specific T RMcells, a role for these cytokines RMresponses against antigens had not studied....
Abstract Resident memory T cells (T RM) are a unique subset of that persist within non-lymphoid tissues. Previous studies have identified RMwithin the brain (bT after peripheral infection and vaccination in mice, with more recent appreciation human tissue. While bT RMare important for protection CNS against reinfection, their heterogeneity at single cell level overall involvement shaping neuroimmune landscape remains unknown. Here, we defined viral-specific RMheterogeneity by RNA sequencing...
ABSTRACT The study of antigen-specific lymphocytes has been a key advancement in immunology the past few decades. development multimerized probes containing antigens, peptide:MHC complexes, or other ligands was one innovation allowing direct by flow cytometry. While these types studies are now common and performed thousands laboratories, quality control assessment probe is often minimal. In fact, many made in-house protocols vary between labs. multimers can be obtained from commercial...
Abstract The shifting paradigm regarding immune surveillance of the central nervous system (CNS) has shed light on cell networks thought to be absent from healthy brain tissue. Resident memory T cells (TRM) are a unique subset that persist within non-lymphoid tissues provide rapid onset protection against reinfection. Recently, TRM (bTRM) have been identified in humans, with CNS or peripheral infection, vaccination leading bTRM establishment mice. While important for reinfection, their...
<h3>Background</h3> Melanoma patients who develop immunotherapy-related adverse events often have durable responses to treatment. We previously identified that long-term melanoma survivors presenting with the autoimmune event, vitiligo, developed long lived CD8+ resident memory T cell (TRM) in skin and tumor circulating (TCIRC) clonal counterparts blood.<sup>1</sup> Despite focus on cells prior studies, CD4+ features remain largely background. <h3>Methods</h3> Using same patient cohort, we...