Characterization of HLA-A*0201 restricted cytotoxic CD8+ T cells directed against ewing tumor specific antigens

CD8+ T cells play a key role in mediating protective immunity after immune challenges such as infection or vaccination. Several subsets of differentiated CD8+ T cells have been identified, however, a deeper understanding of the molecular mechanism that underlies T-cell differentiation is lacking. Conventional approaches to the study of immune responses are typically limited to the analysis of bulk groups of cells that mask the cells’ heterogeneity (RNA-seq, microarray) and to the assessment of a relatively limited number of biomarkers that can be evaluated simultaneously at the population level (flow and mass cytometry). Single-cell analysis, on the other hand, represents a possible alternative that enables a deeper characterization of the underlying cellular heterogeneity. In this study, a murine model was used to characterize immunodominant hemagglutinin (HA533-541)-specific CD8+ T-cell responses to nucleic- and protein-based influenza vaccine candidates, using single-cell sorting followed by transcriptomic analysis. Investigation of single-cell gene expression profiles enabled the discovery of unique subsets of CD8+ T cells that co-expressed cytotoxic genes after vaccination. Moreover, this method enabled the characterization of antigen specific CD8+ T cells that were previously undetected. Single-cell transcriptome profiling has the potential to allow for qualitative discrimination of cells, which could lead to novel insights on biological pathways involved in cellular responses. This approach could be further validated and allow for more informed decision making in preclinical and clinical settings.

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Abstract 1101: Characterization of spatial distribution of tumor-infiltrating CD8+T cells refines their prognostic impact in pancreatic cancer

10.1158/1538-7445.sabcs18-1101 ◽

2019 ◽

Author(s):

Yohei Masugi ◽

Tokiya Abe ◽

Minoru Kitago ◽

Masahiro Shinoda ◽

Michiie Sakamoto

Keyword(s):

Pancreatic Cancer ◽

T Cells ◽

Spatial Distribution ◽

Cd8 T Cells ◽

Prognostic Impact

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Immune characterization of a Colombian familiar cluster of SARS-CoV-2 infection

Biomédica ◽

10.7705/biomedica.5976 ◽

2021 ◽

Vol 41 (Sp. 2) ◽

Author(s):

Wbeimar Aguilar-Jiménez ◽

Lizdany Flórez-Álvarez ◽

Daniel S. Rincón ◽

Damariz Marín-Palma ◽

Alexandra Sánchez-Martínez ◽

...

Keyword(s):

T Cells ◽

Nk Cells ◽

Cd8 T Cells ◽

K562 Cells ◽

Neutralization Assay ◽

Immunological Markers ◽

Hla Dr ◽

Immune Alterations ◽

And Function

Introduction: Immunological markers have been described during COVID-19 and persist after recovery. Those immune alterations are associated with clinical features among SARS-CoV-2 infected individuals. Although, studies reporting a comprehensive analysis of these immune alterations are still limited. Objective: To evaluate the production of pro-inflammatory cytokines, antibody response, and phenotype and function of NK cells and T cells in a Colombian familiar cluster of SARS-CoV-2 infection. Materials and methods: Proinflammatory cytokines were evaluated by RT-PCR and ELISA. Frequency, phenotype and function of NK cells (cocultures with K562 cells) and T-cells (stimulated with Spike/RdRp peptides) were assessed by flow cytometry; anti-SARS-CoV-2 antibodies were determined by indirect immunofluorescence and plaque reduction neutralization assay. Results: During COVID-19, we observed a high pro-inflammatory cytokine production and reduced CD56bright NK cells and cytotoxic response. Compared with healthy controls, infected individuals had a higher frequency of dysfunctional CD8+ T cells CD38+HLA-DR-. During the acute phase, CD8+ T cells stimulated with viral peptides exhibited a monofunctional response characterized by a high IL-10 production. Nevertheless, during recovery, a bifunctional response was observed, characterized by the co-expression of CD107a and Granzyme B or Perforin. Conclusion: Although pro-inflammatory response is a hallmark of SARS-CoV-2 infection, other phenotypic and functional alterations in NK cells and CD8+ T cells could be associated with the outcome of COVID-19. However, additional studies are required to understand these alterations and, to guide future immunotherapy strategies.

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