ABSTRACT
NP105-113-B*07:02-specific CD8+ T cell responses are considered among the most dominant in SARS-CoV-2-infected individuals. We found strong association of this response with mild disease. Analysis of NP105-113-B*07:02-specific T cell clones and single-cell sequencing were performed concurrently, with functional avidity and antiviral efficacy assessed using an in vitro SARS-CoV-2 infection system, and were correlated with T cell receptor usage, transcriptome signature and disease severity (acute n = 77, convalescent n = 52). We demonstrated a beneficial association of NP105-113-B*07:02-specific T cells in COVID-19 disease progression, linked with expansion of T cell precursors, high functional avidity and antiviral effector function. Broad immune memory pools were narrowed postinfection but NP105-113-B*07:02-specific T cells were maintained 6 months after infection with preserved antiviral efficacy to the SARS-CoV-2 Victoria strain, as well as Alpha, Beta, Gamma and Delta variants. Our data show that NP105-113-B*07:02-specific T cell responses associate with mild disease and high antiviral efficacy, pointing to inclusion for future vaccine design.
Subject(s)
HLA-B7 Antigen/immunology , Immunodominant Epitopes/immunology , Nucleocapsid Proteins/immunology , SARS-CoV-2/immunology , T-Lymphocytes, Cytotoxic/immunology , Aged , Amino Acid Sequence , Antibodies, Viral/immunology , Antibody Affinity/immunology , COVID-19/immunology , COVID-19/pathology , Cell Line, Transformed , Female , Gene Expression Profiling , Humans , Immunologic Memory/immunology , Male , Middle Aged , Receptors, Antigen, T-Cell/immunology , Severity of Illness Index , Vaccinia virus/genetics , Vaccinia virus/immunology , Vaccinia virus/metabolismABSTRACT
Recurrent malignant solid pseudopapillary neoplasms of the pancreas (SPNP) are rare tumors with unpredictable clinical and histopathological features. There is a lack of consensus regarding utilization of adjuvant modalities in conjunction with or in lieu of curative metastatectomy. We present a remarkable case where Yttrium-90 selective internal radiation therapy (Y-90 SIRT) was successfully utilized to elucidate underlying tumor biology and aid resection of a large multifocal recurrent metastatic SPNP in the right hemi-liver of a 59-year-old female. Thus, in cases where curative metastatectomy remains the treatment goal in management of recurrent and/or metastatic SPNPs, Y-90 SIRT is a safe and effective adjunct treatment to facilitate curative resection.