Abstract LB-218: High-dimensional modeling of single-cell-based CD8+T cell exhaustion predicts response to immune checkpoint blockade

2019 ◽  
Author(s):  
Guangxu Jin ◽  
Gang Xue ◽  
Rui-Sheng Wang ◽  
Ling-Yun Wu ◽  
Lance Miller ◽  
...  
Keyword(s):  
T Cell ◽  
Single Cell ◽  
Immune Checkpoint ◽  
Cd8 T Cell ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
High Dimensional ◽  
T Cell Exhaustion ◽  
Cell Exhaustion ◽  
Dimensional Modeling

scholarly journals The Potential of T Cell Factor 1 in Sustaining CD8+ T Lymphocyte-Directed Anti-Tumor Immunity

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 515
Author(s):  
Sungmin Jung ◽  
Jea-Hyun Baek
Keyword(s):  
T Cell ◽  
Tumor Immunity ◽  
T Lymphocyte ◽  
Critical Role ◽  
Cd8 T Cell ◽  
Immune Checkpoint Blockade ◽  
Viral Escape ◽  
T Cell Exhaustion ◽  
Cell Exhaustion ◽  
T Cell Factor

T cell factor 1 (TCF1) is a transcription factor that has been highlighted to play a critical role in the promotion of T cell proliferation and maintenance of cell stemness in the embryonic and CD8+ T cell populations. The regulatory nature of TCF1 in CD8+ T cells is of great significance, especially within the context of T cell exhaustion, which is linked to the tumor and viral escape in pathological contexts. Indeed, inhibitory signals, such as programmed cell death 1 (PD-1) and cytotoxic-T-lymphocyte-associated protein 4 (CTLA-4), expressed on exhausted T lymphocytes (TEX), have become major therapeutic targets in immune checkpoint blockade (ICB) therapy. The significance of TCF1 in the sustenance of CTL-mediated immunity against pathogens and tumors, as well as its recently observed necessity for an effective anti-tumor immune response in ICB therapy, presents TCF1 as a potentially significant biomarker and/or therapeutic target for overcoming CD8+ T cell exhaustion and resistance to ICB therapy. In this review, we aim to outline the recent findings on the role of TCF1 in T cell development and discuss its implications in anti-tumor immunity.

scholarly journals B cells sustain inflammation and predict response to immune checkpoint blockade in human melanoma

2018 ◽  
Author(s):  
Johannes Griss ◽  
Wolfgang Bauer ◽  
Christine Wagner ◽  
Margarita Maurer-Granofszky ◽  
Martin Simon ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Immune Checkpoint ◽  
Cd8 T Cell ◽  
Immune Checkpoint Blockade ◽  
Human Melanoma ◽  
Checkpoint Blockade ◽  
Inflammatory Factors ◽  
T Effector Cells

Tumor associated inflammation predicts response to immune checkpoint blockade in human melanoma. Established mechanisms that underlie therapy response and resistance center on anti-tumor T cell responses. Here we show that tumor-associated B cells are vital to tumor associated inflammation. Autologous B cells were directly induced by melanoma conditioned medium, expressed pro- and anti-inflammatory factors, and differentiated towards a plasmablast-like phenotype in vitro. We could identify this phenotype as a distinct cluster of B cells in an independent public single-cell RNA-seq dataset from melanoma tumors. There, plasmablast-like tumor-associated B cells showed expression of CD8+T cell-recruiting chemokines such as CCL3, CCL4, CCL5 and CCL28. Depletion of tumor associated B cells in metastatic melanoma patients by anti-CD20 immunotherapy decreased overall inflammation and CD8+T cell numbers in the human melanoma TME. Conversely, the frequency of plasmablast-like B cells in pretherapy melanoma samples predicted response and survival to immune checkpoint blockade in two independent cohorts. Tumor-associated B cells therefore orchestrate and sustain tumor inflammation, recruit CD8+ T effector cells and may represent a predictor for response and survival to immune checkpoint blockade in human melanoma.

scholarly journals Immune-Checkpoint Blockade Opposes CD8+ T-cell Suppression in Human and Murine Cancer

2019 ◽  
Vol 7 (3) ◽  
pp. 510-525 ◽  
Author(s):  
Lukas W. Pfannenstiel ◽  
C. Marcela Diaz-Montero ◽  
Ye F. Tian ◽  
Joseph Scharpf ◽  
Jennifer S. Ko ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Checkpoint ◽  
Cd8 T Cell ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
T Cell Suppression ◽  
Cell Suppression

scholarly journals A comprehensive single-cell map of T cell exhaustion-associated immune environments in human breast cancer

2022 ◽  
Author(s):  
Sandra Tietscher ◽  
Johanna Wagner ◽  
Tobias Anzeneder ◽  
Claus Langwieder ◽  
Martin Rees ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
T Cell ◽  
Single Cell ◽  
Immune Checkpoint ◽  
Breast Tumors ◽  
Cell Phenotype ◽  
T Cell Exhaustion ◽  
Human Breast ◽  
Cell Exhaustion

Abstract Immune checkpoint therapy in breast cancer remains restricted to triple negative patients, and long-term clinical benefit is rare. The primary aim of immune checkpoint blockade is to prevent or reverse exhausted T cell states, but the causes and implications of T cell exhaustion in breast tumors are not well understood. Here, we used single-cell transcriptomics combined with imaging mass cytometry to comprehensively study exhausted and non-exhausted immune environments in human breast tumors, with a focus on Luminal subtypes. We found that the presence of a PD-1high exhaustion-like T cell phenotype was indicative of an inflammatory immune environment with a characteristic cytotoxic profile and spatial features. Accumulation of natural killer T cells and increased myeloid cell activation in exhausted immune environments provide further support for tissue inflammation in these environments. Consistent with this, our comprehensive map of cellular interactions within the breast tumor microenvironment revealed elevated immunomodulatory, chemotactic, and cytokine signaling in exhausted environments. These data reveal fundamental differences between exhausted and non-exhausted immune environments within Luminal breast cancer, and show that expression of PD-1 and CXCL13 on T cells, and MHC-I – but not PD-L1 – on tumor cells are strong distinguishing features between these environments; these factors are potential new biomarkers for patient stratification.

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