scholarly journals Tumor-expressed immune checkpoint B7x promotes cancer progression and antigen-specific CD8 T cell exhaustion and suppressive innate immune cells

Oncotarget ◽  
2017 ◽  
Vol 8 (47) ◽  
pp. 82740-82753 ◽  
Author(s):  
Kim C. Ohaegbulam ◽  
Weifeng Liu ◽  
Hyungjun Jeon ◽  
Steven C. Almo ◽  
Xingxing Zang
Keyword(s):  
T Cell ◽  
Cancer Progression ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Cd8 T Cell ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
T Cell Exhaustion ◽  
Cell Exhaustion

scholarly journals Antiviral memory CD8 T-cell differentiation, maintenance, and secondary expansion occur independently of MyD88

Blood ◽  
2011 ◽  
Vol 117 (11) ◽  
pp. 3123-3130 ◽  
Author(s):  
Adeeb H. Rahman ◽  
Ruan Zhang ◽  
Christopher D. Blosser ◽  
Baidong Hou ◽  
Anthony L. DeFranco ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Immune Cells ◽  
Cell Expansion ◽  
Cd8 T Cell ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Memory Cd8 T Cells ◽  
T Cell Expansion

Abstract Inflammatory signals induced during infection regulate T-cell expansion, differentiation, and memory formation. Toll-like receptors (TLRs) are inflammatory mediators that allow innate immune cells to recognize and respond to invading pathogens. In addition to their role in innate immune cells, we have found that signals delivered through the TLR adapter protein myeloid differentiation protein 88 (MyD88) play a critical, T cell–intrinsic role in supporting the survival and accumulation of antigen-specific effector cells after acute viral infection. However, the importance of MyD88-dependent signals in regulating the generation and maintenance of memory T cells remained unclear. To address this, we used a novel, inducible knockout system to examine whether MyD88 is required for optimal memory CD8 T-cell generation and responses after lymphocytic choriomeningitis virus infection. We show that whereas MyD88 is critical for initial T-cell expansion, it is not required for the subsequent differentiation and stable maintenance of a memory T-cell population. Furthermore, in contrast to naive CD8 T cells, memory CD8 T cells do not depend on MyD88 for their secondary expansion. Our findings clarify the importance of MyD88 during distinct phases of the antiviral T-cell response and establish differential dependence on MyD88 signaling as a novel characteristic that distinguishes naive from memory CD8 T cells.

scholarly journals Exploring Markers of Exhausted CD8 T Cells to Predict Response to Immune Checkpoint Inhibitor Therapy for Hepatocellular Carcinoma

Liver Cancer ◽  
2021 ◽  
pp. 1-14
Author(s):  
Chia-Lang Hsu ◽  
Da-Liang Ou ◽  
Li-Yuan Bai ◽  
Chia-Wei Chen ◽  
Li Lin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cell ◽  
Tumor Microenvironment ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Cd8 T Cell ◽  
Gene Signature ◽  
T Cell Exhaustion ◽  
Cell Exhaustion

<b><i>Background:</i></b> Reversal of CD8 T-cell exhaustion was considered a major antitumor mechanism of anti-programmed cell death-1 (PD-1)/ anti-programmed death ligand-1 (PD-L1)-based immune checkpoint inhibitor (ICI) therapy. <b><i>Objectives:</i></b> The aim of this study was to identify markers of T-cell exhaustion that is best associated with ICI treatment efficacy for advanced hepatocellular carcinoma (HCC). <b><i>Methods:</i></b> Immune cell composition of archival tumor samples was analyzed by transcriptomic analysis and multiplex immunofluorescence staining. <b><i>Results:</i></b> HCC patients with objective response after anti-PD-1/anti-PD-L1-based ICI therapy (<i>n</i> = 42) had higher expression of genes related to T-cell exhaustion. A 9-gene signature (LAG3, CD244, CCL5, CXCL9, CXCL13, MSR1, CSF3R, CYBB, and KLRK1) was defined, whose expression was higher in patients with response to ICI therapy, correlated with density of CD8<sup>+</sup>LAG3<sup>+</sup> cells in tumor microenvironment, and independently predicted better progression-free and overall survival. This 9-gene signature had similar predictive values for patients who received single-agent or combination ICI therapy and was not associated with prognosis in HCC patients who received surgery, suggesting that it may outperform other T-cell signatures for predicting efficacy of ICI therapy for HCC. For HCC patients who underwent surgery for both the primary liver and metastatic lung tumors (<i>n</i> = 31), lung metastatic HCC was associated with a higher exhausted CD8 T-cell signature, consistent with prior observation that patients with lung metastatic HCC may have higher probability of response to ICI therapy. <b><i>Conclusions:</i></b> CD8 T-cell exhaustion in tumor microenvironment may predict better efficacy of ICI therapy for HCC.

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 Innate Immune Cells and Their Contribution to T-Cell-Based Immunotherapy

2020 ◽  
Vol 21 (12) ◽  
pp. 4441 ◽  
Author(s):  
Pierpaolo Ginefra ◽  
Girieca Lorusso ◽  
Nicola Vannini
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cancer Immunotherapy ◽  
Cancer Patients ◽  
Immune Cells ◽  
Adoptive Cell Therapy ◽  
Adaptive Immune Response ◽  
Immune Checkpoint Blockade ◽  
Innate Immune ◽  
Innate Immune Cells

In recent years, immunotherapy has become the most promising therapy for a variety of cancer types. The development of immune checkpoint blockade (ICB) therapies, the adoptive transfer of tumor-specific T cells (adoptive cell therapy (ACT)) or the generation of T cells engineered with chimeric antigen receptors (CAR) have been successfully applied to elicit durable immunological responses in cancer patients. However, not all the patients respond to these therapies, leaving a consistent gap of therapeutic improvement that still needs to be filled. The innate immune components of the tumor microenvironment play a pivotal role in the activation and modulation of the adaptive immune response against the tumor. Indeed, several efforts are made to develop strategies aimed to harness innate immune cells in the context of cancer immunotherapy. In this review, we describe the contribution of innate immune cells in T-cell-based cancer immunotherapy and the therapeutic approaches implemented to broaden the efficacy of these therapies in cancer patients.

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