Targeted dual biologic therapy for erythroderma of unknown etiology guided by high-parameter peripheral blood immunophenotyping.

Erythroderma is a severe and heterogeneous inflammatory skin condition with little guidance on the approach to management in cases of unknown etiology. To guide therapeutic selection, we sought to create an immunophenotyping platform able to identify aberrant cell populations and cytokines in subtypes of erythroderma. We performed high-parameter flow cytometry on peripheral blood mononuclear cells (PBMCs) and whole blood of a patient with refractory idiopathic erythroderma, erythrodermic patients with Sézary syndrome and pityriasis rubra pilaris, and healthy controls.

Bivalent mRNA COVID vaccines elicit predominantly cross-reactive CD4 T cell clonotypes.

Bivalent COVID vaccines containing mRNA for ancestral and Omicron BA.5 spike proteins do not induce stronger T cell responses to Omicron BA.5 spike proteins than monovalent vaccines that contain only ancestral spike mRNA.

Proviral location affects cognate peptide-induced virus production and immune recognition of HIV-1-infected T cell clones.

BACKGROUNDHIV-1-infected CD4+ T cells contribute to latent reservoir persistence by proliferating while avoiding immune recognition. Integration features of intact proviruses in elite controllers (ECs) and people on long-term therapy suggest that proviruses in specific chromosomal locations can evade immune surveillance. However, direct evidence of this mechanism is missing.

Distinct Myeloid Derived Suppressor Cell Populations Promote Tumor Aggression in Glioblastoma.

Unlabelled: The diversity of genetic programs and cellular plasticity of glioma-associated myeloid cells, and thus their contribution to tumor growth and immune evasion, is poorly understood. We performed single cell RNA-sequencing of immune and tumor cells from 33 glioma patients of varying tumor grades. We identified two populations characteristic of myeloid derived suppressor cells (MDSC), unique to glioblastoma (GBM) and absent in grades II and III tumors: i) an early progenitor population (E-MDSC) characterized by strong upregulation of multiple catabolic, anabolic, oxidative stress, and hypoxia pathways typically observed within tumor cells themselves, and ii) a monocytic MDSC (M-MDSC) population.

Engineered human cytokine/antibody fusion proteins expand regulatory T cells and confer autoimmune disease protection.

Low-dose human interleukin-2 (hIL-2) treatment is used clinically to treat autoimmune disorders due to the cytokine's preferential expansion of immunosuppressive regulatory T cells (Tregs). However, off-target immune cell activation and short serum half-life limit the clinical potential of IL-2 treatment. Recent work showed that complexes comprising hIL-2 and the anti-hIL-2 antibody F5111 overcome these limitations by preferentially stimulating Tregs over immune effector cells.

SARS-CoV-2 vaccination diversifies the CD4+ spike-reactive T cell repertoire in patients with prior SARS-CoV-2 infection.

Background: COVID-19 mRNA vaccines elicit strong T and B cell responses to the SARS-CoV-2 spike glycoprotein in both SARS-CoV-2 naïve and experienced patients. However, it is unknown whether the post-vaccine CD4+ T cell responses seen in patients with a history of COVID-19 are due to restimulation of T cell clonotypes that were first activated during natural infection or if they are the result of new clones activated by the vaccine.

Methods: To address this question, we analyzed the SARS-CoV-2 spike glycoprotein-specific CD4+ T cell receptor repertoire before and after vaccination in 10 COVID-19 convalescent patients and 4 SARS-CoV-2 naïve healthy donor vaccine recipients.

SARS-CoV-2-specific immune responses in boosted vaccine recipients with breakthrough infections during the Omicron variant surge.

BackgroundBreakthrough SARS-CoV-2 infections in vaccinated individuals have been previously associated with suboptimal humoral immunity. However, less is known about breakthrough infections with the Omicron variant.MethodsWe analyzed SARS-CoV-2-specific antibody and cellular responses in healthy vaccine recipients who experienced breakthrough infections a median of 50 days after receiving a booster mRNA vaccine with an ACE2 binding inhibition assay and an ELISpot assay, respectively.

CD4+ T cells from COVID-19 mRNA vaccine recipients recognize a conserved epitope present in diverse coronaviruses.

Recent studies have shown that vaccinated individuals harbor T cells that can cross-recognize SARS-CoV-2 and endemic human common cold coronaviruses. However, it is still unknown whether CD4+ T cells from vaccinated individuals recognize peptides from bat coronaviruses that may have the potential of causing future pandemics. In this study, we identified a SARS-CoV-2 spike protein epitope (S815-827) that is conserved in coronaviruses from different genera and subgenera, including SARS-CoV, MERS-CoV, multiple bat coronaviruses, and a feline coronavirus.

Transcriptional programs of neoantigen-specific TIL in anti-PD-1-treated lung cancers.

PD-1 blockade unleashes CD8 T cells, including those specific for mutation-associated neoantigens (MANA), but factors in the tumour microenvironment can inhibit these T cell responses. Single-cell transcriptomics have revealed global T cell dysfunction programs in tumour-infiltrating lymphocytes (TIL). However, the majority of TIL do not recognize tumour antigens, and little is known about transcriptional programs of MANA-specific TIL.

Functional characterization of CD4+ T cell receptors crossreactive for SARS-CoV-2 and endemic coronaviruses.

BACKGROUNDRecent studies have reported T cell immunity to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in unexposed donors, possibly due to crossrecognition by T cells specific for common cold coronaviruses (CCCs). True T cell crossreactivity, defined as the recognition by a single TCR of more than one distinct peptide-MHC ligand, has never been shown in the context of SARS-CoV-2.METHODSWe used the viral functional expansion of specific T cells (ViraFEST) platform to identify T cell responses crossreactive for the spike (S) glycoproteins of SARS-CoV-2 and CCCs at the T cell receptor (TCR) clonotype level in convalescent COVID-19 patients (CCPs) and SARS-CoV-2-unexposed donors.

Student Perceptions of M.D.-Ph.D. Programs: A Qualitative Identification of Barriers Facing Prospective M.D.-Ph.D. Applicants.

Despite a high degree of interest in research among matriculating M.D. students, very few apply to combined M.

An adapted anti-CTLA4 therapeutic aimed at mitigating the toxicities of checkpoint inhibition.

Antibodies that target immune checkpoint molecules, such as CTLA4, provide robust antitumor effects in a subset of patients. Unfortunately, not all patients respond to immune checkpoint inhibition, and some develop life-threatening immune-related adverse events (irAEs). The mechanisms that underlie irAEs from immune checkpoint inhibition are not fully understood, and treatment strategies are currently limited to targeting inflammatory mediators.