scholarly journals Discipline in Stages: Regulating CD8+ Resident Memory T Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Rut Mora-Buch ◽  
Shannon K. Bromley
Keyword(s):  
T Cells ◽  
Transcriptional Networks ◽  
Peripheral Tissues ◽  
Local Protection ◽  
Control Tumor Growth ◽  
Cognate Antigen ◽  
Control Tumor ◽  
Checkpoint Receptors ◽  
Resident Memory T Cells ◽  
And Control

Resident memory CD8+ T (TRM) cells are a lymphocyte lineage distinct from circulating memory CD8+ T cells. TRM lodge within peripheral tissues and secondary lymphoid organs where they provide rapid, local protection from pathogens and control tumor growth. However, dysregulation of CD8+ TRM formation and/or activation may contribute to the pathogenesis of autoimmune diseases. Intrinsic mechanisms, including transcriptional networks and inhibitory checkpoint receptors control TRM differentiation and response. Additionally, extrinsic stimuli such as cytokines, cognate antigen, fatty acids, and damage signals regulate TRM formation, maintenance, and expansion. In this review, we will summarize knowledge of CD8+ TRM generation and highlight mechanisms that regulate the persistence and responses of heterogeneous TRM populations in different tissues and distinct microenvironments.

scholarly journals EXTH-43. GENERATION OF A B-CELL-BASED VACCINE FOR THE TREATMENT OF GLIOBLASTOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii96-ii96
Author(s):  
Catalina Lee Chang ◽  
Jason Miska ◽  
David Hou ◽  
Aida Rashidi ◽  
Peng Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell ◽  
T Cell Activation ◽  
Cd8 T Cells ◽  
Cell Activation ◽  
Cross Presentation ◽  
Control Tumor Growth ◽  
Efficient Alternative ◽  
Control Tumor ◽  
Secondary Lymphoid Organs

Abstract Immunotherapy has revolutionized the treatment of many tumors. However, most glioblastoma (GBM) patients have not, so far, benefited from such successes. With the goal of exploring ways to boost anti-GBM immunity, we developed a B-cell-based vaccine (BVax) that consists of 4-1BBL+ B cells activated with CD40 agonism and IFNg stimulation. BVaxmigrate to key secondary lymphoid organs and are proficient at antigen cross-presentation, which promotes both the survival and functionality of CD8+ T cells. A combination of radiation, BVax, and PD-L1 blockade conferred tumor eradication in 80% of treated tumor-bearing animals. This treatment elicited immunologic memory that prevented the growth of new tumors upon subsequent re-injection in cured mice. GBM patient-derived BVax were successful in activating autologous CD8+ T cells; these T cells showed a strong ability to kill autologous glioma cells. In addition to the role in activating CD8+ T cells, BVax produce tumor-specific antibodies able to control tumor growth via antibody-mediated cell cytotoxicity. In conclusion, BVax tackles GBM immunosurveillance escape by using both cellular (CD8+ T-cell activation) and humoral (anti-tumor antibody production) immunity. Our study provides an efficient alternative to current immunotherapeutic approaches that can be readily translated to the clinic.

scholarly journals Skin-Resident Memory T Cells: Pathogenesis and Implication for the Treatment of Psoriasis

2021 ◽  
Vol 10 (17) ◽  
pp. 3822
Author(s):  
Trung T. Vu ◽  
Hanako Koguchi-Yoshioka ◽  
Rei Watanabe
Keyword(s):  
T Cells ◽  
Memory T Cells ◽  
Inflammatory Diseases ◽  
Adaptive Immune Response ◽  
Psoriatic Skin ◽  
Peripheral Tissues ◽  
Potential Index ◽  
Circulating T Cells ◽  
Chronic Skin ◽  
Resident Memory T Cells

Tissue-resident memory T cells (TRM) stay in the peripheral tissues for long periods of time, do not recirculate, and provide the first line of adaptive immune response in the residing tissues. Although TRM originate from circulating T cells, TRM are physiologically distinct from circulating T cells with the expression of tissue-residency markers, such as CD69 and CD103, and the characteristic profile of transcription factors. Besides defense against pathogens, the functional skew of skin TRM is indicated in chronic skin inflammatory diseases. In psoriasis, IL-17A-producing CD8+ TRM are regarded as one of the pathogenic populations in skin. Although no licensed drugs that directly and specifically inhibit the activity of skin TRM are available to date, psoriatic skin TRM are affected in the current treatments of psoriasis. Targeting skin TRM or using TRM as a potential index for disease severity can be an attractive strategy in psoriasis.

scholarly journals CXCR6 governs the retention of tissue-resident memory T cells to promote enhanced surveillance and control of ovarian cancer

2020 ◽  
Author(s):  
Ravikumar Muthuswamy ◽  
AJ Robert McGray ◽  
Sebastiano Battaglia ◽  
Wenjun He ◽  
Anthony Miliotto ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Ovarian Tumor ◽  
Memory T Cells ◽  
Memory Cell ◽  
Tumor Control ◽  
Control Analysis ◽  
Resident Memory T Cells ◽  
And Control

AbstractWhile the beneficial role played by tissue-resident memory T cells (Trm) in tumor control has emerged, the chemotactic mechanisms associated with their localization and retention in the tumor microenvironment (TME) of cancers including ovarian are poorly understood. The current study has identified chemokine receptor CXCR6 as crucial for Trm responses to ovarian cancer by promoting their localization and retention in the ovarian tumor microenvironment. In human ovarian cancer patients, CXCR6 significantly marked CD8+ CD103+ tumor-infiltrating Trm cells. Functional studies in mice revealed high expression of CXCR6 in tumor-specific T cells that reside in tissues, but not by those in circulation. Knockout of CXCR6 in tumor-specific T cells led to a heightened circulatory response in blood, but diminished resident memory cell accumulation in tumors, culminating in poor tumor control. Analysis of Wild type (Wt.) and CXCR6KO (KO) tumor-specific T cells trafficking in recipient mice using bioluminescent imaging revealed that compared to Wt., KO T cells preferentially localized to the spleen, indicating the possibility of reduced retention in tumor tissues. These findings indicate that CXCR6 by mediating increased retention of tumor-specific T cells in the ovarian tumor microenvironment, promotes resident memory T cell-mediated surveillance and control of ovarian cancer.

scholarly journals Combination rhIL-15 and Anti-PD-L1 (Avelumab) Enhances HIVGag-Specific CD8 T-Cell Function

2020 ◽  
Vol 222 (9) ◽  
pp. 1540-1549
Author(s):  
Bruktawit A Goshu ◽  
Hui Chen ◽  
Maha Moussa ◽  
Jie Cheng ◽  
Marta Catalfamo
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cell Function ◽  
Cd8 T Cell ◽  
Peripheral Tissues ◽  
T Cell Function ◽  
Interleukin 15 ◽  
Checkpoint Receptors

Abstract In chronic HIV infection, virus-specific cytotoxic CD8 T cells showed expression of checkpoint receptors and impaired function. Therefore, restoration of CD8 T-cell function is critical in cure strategies. Here, we show that in vitro blockade of programmed cell death ligand 1 (PD-L1) by an anti-PD-L1 antibody (avelumab) in combination with recombinant human interleukin-15 (rhIL-15) synergistically enhanced cytokine secretion by proliferating HIVGag-specific CD8 T cells. In addition, these CD8 T cells have a CXCR3+PD1−/low phenotype, suggesting a potential to traffic into peripheral tissues. In vitro, proliferating CD8 T cells express PD-L1 suggesting that anti-PD-L1 treatment also targets virus-specific CD8 T cells. Together, these data indicate that rhIL-15/avelumab combination therapy could be a useful strategy to enhance CD8 T-cell function in cure strategies.

scholarly journals Erratum: Programs for the persistence, vigilance and control of human CD8+ lung-resident memory T cells

2017 ◽  
Vol 18 (2) ◽  
pp. 246-246 ◽  
Author(s):  
Pleun Hombrink ◽  
Christina Helbig ◽  
Ronald A Backer ◽  
Berber Piet ◽  
Anna E Oja ◽  
...  
Keyword(s):  
T Cells ◽  
Memory T Cells ◽  
Resident Memory T Cells ◽  
And Control

scholarly journals Resident Memory T Cells and Their Role within the Liver

2020 ◽  
Vol 21 (22) ◽  
pp. 8565
Author(s):  
Sonia Ghilas ◽  
Ana-Maria Valencia-Hernandez ◽  
Matthias H. Enders ◽  
William R. Heath ◽  
Daniel Fernandez-Ruiz
Keyword(s):  
T Cells ◽  
Memory T Cells ◽  
Plasmodium Species ◽  
Immunological Memory ◽  
Cellular Responses ◽  
The Body ◽  
Entire Body ◽  
Memory Cells ◽  
Peripheral Tissues ◽  
Resident Memory T Cells

Immunological memory is fundamental to maintain immunity against re-invading pathogens. It is the basis for prolonged protection induced by vaccines and can be mediated by humoral or cellular responses—the latter largely mediated by T cells. Memory T cells belong to different subsets with specialized functions and distributions within the body. They can be broadly separated into circulating memory cells, which pace the entire body through the lymphatics and blood, and tissue-resident memory T (TRM) cells, which are constrained to peripheral tissues. Retained in the tissues where they form, TRM cells provide a frontline defense against reinfection. Here, we review this population of cells with specific attention to the liver, where TRM cells have been found to protect against infections, in particular those by Plasmodium species that cause malaria.

Expression pattern of tissue-resident memory T cells in cutaneous lupus erythematosus

Lupus ◽  
2021 ◽  
pp. 096120332110172
Author(s):  
Hyeon-Jung Gu ◽  
Shinyoung Song ◽  
Joo Young Roh ◽  
YunJae Jung ◽  
Hee Joo Kim
Keyword(s):  
T Cells ◽  
Lupus Erythematosus ◽  
Memory T Cells ◽  
Cutaneous Lupus Erythematosus ◽  
Discoid Lupus Erythematosus ◽  
Type I ◽  
Systemic Lupus ◽  
Peripheral Tissues ◽  
Resident Memory T Cells ◽  
Cutaneous Lupus

Background Tissue resident memory T cells (TRMs) persist long-term in peripheral tissues without recirculation, triggering an immediate protective inflammatory state upon the re-recognition of the antigen. Despite evidence incriminating the dysregulation of TRMs in autoimmune diseases, few studies have examined their expression in cutaneous lupus erythematosus (CLE). Objectives We aimed to examine whether there are differences among TRM populations in CLE depending on different clinical conditions, such as the CLE subtype or association with systemic lupus erythematosus, and to determine the effect of type I interferon (IFN) on the development of TRMs in CLE. Methods CLE disease activity was evaluated using the Cutaneous Lupus Erythematosus Disease Area and Severity Index. The expression of the TRM markers CD69 and CD103 in CLE lesions was evaluated by immunofluorescence. Flow cytometry was performed on peripheral blood mononuclear cells after IFNα treatment. Results The number of TRMs expressing either CD69 or CD103 was significantly higher in CLE lesions than in control skin; however, it was not significantly different between discoid lupus erythematosus and subacute CLE, or dependent on the presence of concomitant systemic lupus. Lesional severity was not correlated with an increase in TRMs in CLE. IFNα treatment induced a conspicuous increase in CD69 expression in skin-homing T cells, more profoundly in CD4+ T cells than in CD8+ T cells. Conclusions Skin TRMs, either CD69 or CD103-positive cells, showed increased levels in the lesional skin of CLE, and IFNα increased the expression of CD69 in T cells.

scholarly journals VLM catecholaminergic neurons control tumor growth by regulating CD8+ T cells

2021 ◽  
Vol 118 (28) ◽  
pp. e2103505118
Author(s):  
Ze Zhang ◽  
Yehua Li ◽  
Xueyuan Lv ◽  
Linlin Zhao ◽  
Xiaodong Wang
Keyword(s):  
T Cells ◽  
Nervous System ◽  
Tumor Growth ◽  
Mouse Brain ◽  
Adaptive Immune System ◽  
Ventrolateral Medulla ◽  
Mouse Tumor ◽  
Control Tumor Growth ◽  
The Central Nervous System ◽  
Control Tumor

It is known that tumor growth can be influenced by the nervous system. It is not known, however, if tumors communicate directly with the central nervous system (CNS) or if such interactions may impact tumor growth. Here, we report that ventrolateral medulla (VLM) catecholaminergic (CA) neurons in the mouse brain are activated in tumor-bearing mice and the activity of these neurons significantly alter tumor growth in multiple syngeneic and spontaneous mouse tumor models. Specific ablation of VLM CA neurons by a dopamine-β-hydroxylase (DBH) promotor-activated apoptosis-promoting caspase-3 in Dbh-Cre mice as well as inhibition of these neurons by a chemogenetic method slowed tumor progression. Consistently, chemogenetic activation of VLM CA neurons promoted tumor growth. The tumor inhibition effect of VLM CA neuron ablation is mitigated in Dbh-Cre;Rag1−/− mice, indicating that this regulatory effect is mediated by the adaptive immune system. Specific depletion of CD8+ T cells using an anti-CD8+ antibody also mitigated the tumor suppression resulting from the VLM CA neuron ablation. Finally, we showed that the VLM CA neuronal ablation had an additive antitumor effect with paclitaxel treatment. Collectively, our study uncovered the role of VLM CA neurons in the mouse brain in controlling tumor growth in the mouse body.

Sequence of αPD-1 relative to local tumor irradiation determines the induction of abscopal antitumor immune responses

2021 ◽  
Vol 6 (58) ◽  
pp. eabg0117
Author(s):  
Joyce Wei ◽  
Welby Montalvo-Ortiz ◽  
Lola Yu ◽  
Amanda Krasco ◽  
Sarah Ebstein ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Local Tumor ◽  
Tumor Irradiation ◽  
Treatment Conditions ◽  
Distal Tumor ◽  
Control Tumor Growth ◽  
Potential Synergy ◽  
Control Tumor

Although radiotherapy has been used for over a century to locally control tumor growth, alone it rarely induces an abscopal response or systemic antitumor immunity capable of inhibiting distal tumors outside of the irradiation field. Results from recent studies suggest that combining immune checkpoint blockades to radiotherapy may enhance abscopal activity. However, the treatment conditions and underlying immune mechanisms that consistently drive an abscopal response during radiation therapy combinations remain unknown. Here, we analyzed the antitumor responses at primary and distal tumor sites, demonstrating that the timing of αPD-1 antibody administration relative to radiotherapy determined the potency of the induced abscopal response. Blockade of the PD-1 pathway after local tumor irradiation resulted in the expansion of polyfunctional intratumoral CD8+ T cells, a decrease in intratumoral dysfunctional CD8+ T cells, expansion of reprogrammable CD8+ T cells, and induction of potent abscopal responses. However, administration of αPD-1 before irradiation almost completely abrogated systemic immunity, which associated with increased radiosensitivity and death of CD8+ T cells. The subsequent reduction of polyfunctional effector CD8+ T cells at the irradiated tumor site generated a suboptimal systemic antitumor response and the loss of abscopal responses. Therefore, this report maximizes the potential synergy between radiotherapy and αPD-1 immunotherapy, information that will benefit clinical combinations of radiotherapy and immune checkpoint blockade.

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