scholarly journals Increased expression of immune checkpoint programmed cell death protein‐1 ( PD ‐1) on T cell subsets of bone marrow aspirates in patients with B‐Lymphoblastic leukemia, especially in relapse and at diagnosis

2020 ◽  
Vol 98 (4) ◽  
pp. 336-347 ◽  
Author(s):  
Sang Hyuk Park ◽  
Eunkyoung You ◽  
Chan‐Jeoung Park ◽  
Young‐Uk Cho ◽  
Seongsoo Jang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Death ◽  
T Cell ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Lymphoblastic Leukemia ◽  
T Cell Subsets ◽  
Cell Death Protein

scholarly journals Immune Checkpoint Programmed Cell Death Protein-1 (PD-1) Expression on Bone Marrow T Cell Subsets in Patients With Plasma Cell Myeloma

2021 ◽  
Vol 41 (3) ◽  
pp. 259-267
Author(s):  
Min Young Lee ◽  
Chan-Jeoung Park ◽  
Young-Uk Cho ◽  
Eunkyoung You ◽  
Seongsoo Jang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Death ◽  
T Cell ◽  
Programmed Cell Death ◽  
Plasma Cell ◽  
Immune Checkpoint ◽  
T Cell Subsets ◽  
Plasma Cell Myeloma ◽  
Cell Death Protein

scholarly journals Immune checkpoint dysfunction in large and medium vessel vasculitis

2017 ◽  
Vol 312 (5) ◽  
pp. H1052-H1059 ◽  
Author(s):  
Ryu Watanabe ◽  
Hui Zhang ◽  
Gerald Berry ◽  
Jörg J. Goronzy ◽  
Cornelia M. Weyand
Keyword(s):  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Intimal Hyperplasia ◽  
Cd4 T Cells ◽  
Vessel Wall ◽  
Checkpoint Inhibitors ◽  
Cell Death Protein

Giant cell arteritis (GCA) is a granulomatous vasculitis of the aorta and its medium-sized branch vessels. CD4 T cells, macrophages, and dendritic cells (DCs) build granulomatous infiltrates that injure the vessel wall and elicit a maladaptive response to injury. Pathological consequences include fragmentation of elastic membranes, destruction of the medial layer, microvascular neoangiogenesis, massive outgrowth of myofibroblasts, and lumen-occlusive intimal hyperplasia. Antigens have been suspected to drive the local activation of vasculitogenic CD4 T cells, but recent data have suggested a more generalized defect in the threshold setting of such T cells, rendering them hyperreactive. Under physiological conditions, immune checkpoints provide negative signals to curb T cell activation and prevent inflammation-associated tissue destruction. This protective mechanism is disrupted in GCA. Vessel wall DCs fail to express the immunoinhibitory ligand programmed cell death ligand-1, leaving lesional T cells unchecked. Consequently, programmed cell death protein-1-positive CD4 T cells can enter the immunoprivileged vessel wall, where they produce a broad spectrum of inflammatory cytokines (interferon-γ, IL-17, and IL-21) and have a direct role in driving intimal hyperplasia and intramural neoangiogenesis. The deficiency of the programmed cell death protein-1 immune checkpoint in GCA, promoting unopposed T cell immunity, contrasts with checkpoint hyperactivity in cancer patients in whom excessive programmed cell death ligand-1 expression paralyzes the function of antitumor T cells. Excessive checkpoint activity is the principle underlying cancer-immune evasion and is therapeutically targeted by immunotherapy with checkpoint inhibitors. Such checkpoint inhibitors, which unleash anticancer T cells and induce immune-related toxicity, may lead to drug-induced vasculitis.

scholarly journals Anti-PD-1 Therapy-Associated Perforating Colitis

2018 ◽  
Vol 2018 ◽  
pp. 1-3 ◽  
Author(s):  
Romulo Celli ◽  
Harriet M. Kluger ◽  
Xuchen Zhang
Keyword(s):  
Cell Death ◽  
T Cell ◽  
Programmed Cell Death ◽  
Adverse Effects ◽  
T Lymphocyte ◽  
Immune Checkpoint ◽  
Cytotoxic T Lymphocyte ◽  
Colonic Perforation ◽  
Advanced Malignancies ◽  
Cell Death Protein

Inhibition of immune checkpoint T cell regulatory molecules by using programmed cell death protein 1 (PD-1), or its ligand (PDL-1), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) has been increasingly used to treat advanced malignancies. The immune-related adverse effects associated with these treatments such as diarrhea, colitis, and CTLA-4 treatment-associated perforating colitis have been reported. However, anti-PD-1/PD-L1-associated perforating colitis has rarely been reported. We report a case of colonic perforation in a patient recently treated with pembrolizumab, a PD-1 inhibitor for metastatic melanoma. Awareness of anti-PD-1/PD-L1-associated colitis and perforation will facilitate a timely diagnosis and management as they are increasingly used in oncology.

scholarly journals Interleukin-4 induces programmed cell death (apoptosis) in cases of high-risk acute lymphoblastic leukemia

Blood ◽  
1994 ◽  
Vol 83 (7) ◽  
pp. 1731-1737 ◽  
Author(s):  
A Manabe ◽  
E Coustan-Smith ◽  
M Kumagai ◽  
FG Behm ◽  
SC Raimondi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Death ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Programmed Cell Death ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Fatal Outcome ◽  
Interleukin 4 ◽  
B Lineage

Abstract We investigated the effects of interleukin-4 (IL-4) on the survival of leukemic and normal B-cell progenitors cultured on bone marrow stroma. IL-4 (at 100 U/mL) was cytotoxic in 16 of 21 cases of B-lineage acute lymphoblastic leukemia, causing reductions in CD19+ cell numbers that ranged from 50% to greater than 99% (median 83.5%) of those in parallel cultures not exposed to the cytokine. All nine cases with the t(9;22)(q34;q11) or the t(4;11)(q21;q23), chromosomal features that are often associated with multidrug resistance and a fatal outcome, were susceptible to IL-4 toxicity. IL-4 cytotoxicity resulted from induction of programmed cell death (apoptosis); there was no evidence of cell killing mediated by T, natural killer, or stromal cells. IL-4 cytotoxicity extended to a proportion of normal B-cell progenitors. After 7 days of culture with IL-4 at 100 U/mL, fewer CD19+, CD34+ normal lymphoblasts (the most immature subset) survived: in five experiments the mean (+/- SEM) reduction in cell recoveries caused by IL-4 was 60.0% +/- 6.0%. By contrast, reductions in recovery of more differentiated bone marrow B cells (CD19+, CD34-, surface Ig+) were low (6.6% +/- 2.2%; P < .001 by t-test). Our findings indicate that IL-4 is cytotoxic for human B-cell precursors and support clinical testing of IL-4 in cases of high-risk lymphoblastic leukemia resistant to conventional therapy.

scholarly journals High CD3 and ICOS and low TIM-3 expression predict favourable survival in resected oesophageal squamous cell carcinoma

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Min Hee Hong ◽  
Su-Jin Shin ◽  
Sung Kwan Shin ◽  
Dae Joon Kim ◽  
Jae Ill Zo ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Death ◽  
T Cell ◽  
Programmed Cell Death ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Lymphocyte Activation ◽  
Tissue Microarrays ◽  
T Cell Subsets ◽  
Oesophageal Squamous Cell Carcinoma

AbstractWith the increasing oncological potential of immunotherapy, several immune checkpoint modulators are being investigated. The value of immune markers, including programmed cell death ligand-1, programmed cell death-1 (PD-1), inducible co-stimulator (ICOS), lymphocyte activation gene-3, T-cell immunoglobulin, and mucin-dominant containing-3 (TIM-3), is not well known. Using tissue microarrays of 396 patients who underwent surgery for oesophageal squamous cell carcinoma (ESCC), infiltrated T-cell subsets (CD3, CD8, and Foxp3) and checkpoint protein expression were scored. With a median follow-up of 24.8 months, CD3+ TIL subsets (50.0%) had longer median recurrence-free survival (RFS, 55.0 vs 21.4 months) and overall survival (OS, 77.7 vs 35.8 months). Patients with high ICOS expression (46.5%) had longer median RFS (53.9 vs 25.3 months) and OS (88.8 vs 36.9 months). For PD-1, RFS (hazard ratio [HR] 0.67) and OS (HR 0.66) were significantly longer in the high-expression group (45.2%). In the multivariate analysis, high TIM-3 expression (50.8%) had a significant relationship with shorter RFS (HR = 1.52) and OS (HR = 1.60). High CD3+ TIL and T-cell ICOS expression were associated with favourable prognosis, whereas high TIM-3 expression suggested a poor prognosis. Our findings may confer new insights to improve ESCC outcomes beyond the application of PD-1 blockade.

scholarly journals Immune Thrombocytopenia Induced by Immune Checkpoint Inhibitrs in Lung Cancer: Case Report and Literature Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Wang Xie ◽  
NaNa Hu ◽  
LeJie Cao
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Clinical Presentation ◽  
Checkpoint Inhibitors ◽  
Immune Dysregulation ◽  
Cancer Case ◽  
Severe Thrombocytopenia ◽  
Cell Death Protein

Immune checkpoint inhibitors (ICIs), including antibodies targeting programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1), are being extensively used on advanced human malignancies therapy. The treatment with ICIs have acquired durable tumor inhibition and changed the treatment landscape in lung cancer. Immune-related adverse events including pneumonitis and thyroiditis have been well described, but less frequent events, such as ICIs-induced thrombocytopenia, are now emerging and may sometimes be severe or fatal. Since early detection and prompt intervention are crucial to prevent fatal consequences, it is of outmost importance that medical staff is aware of these potential toxicities and learn to recognize and treat them adequately. This review focuses on the epidemiology, clinical presentation, mechanisms, and clinical management of ICIs-induced thrombocytopenia in patients with lung cancer. We also present a patient with advanced lung adenocarcinoma who received the PD-L1 inhibitor atezolizumab and eventually developed severe thrombocytopenia. The case indirectly suggests that cytokine changes might contribute to immune dysregulation in ICIs-induced thrombocytopenia.

scholarly journals Molecular dynamics of the immune checkpoint programmed cell death protein I, PD-1: conformational changes of the BC-loop upon binding of the ligand PD-L1 and the monoclonal antibody nivolumab

2020 ◽  
Vol 21 (S17) ◽  
Author(s):  
Bernhard Roither ◽  
Chris Oostenbrink ◽  
Wolfgang Schreiner
Keyword(s):  
Molecular Dynamics ◽  
Signal Transduction ◽  
T Cells ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Conformational Changes ◽  
Immune Checkpoint ◽  
Active Conformation ◽  
Dynamics Simulations ◽  
Cell Death Protein

Abstract Background The immune checkpoint receptor programmed cell death protein I (PD-1) has been identified as a key target in immunotherapy. PD-1 reduces the risk of autoimmunity by inducing apoptosis in antigen-specific T cells upon interaction with programmed cell death protein ligand I (PD-L1). Various cancer types overexpress PD-L1 to evade the immune system by inducing apoptosis in tumor-specific CD8+ T cells. The clinically used blocking antibody nivolumab binds to PD-1 and inhibits the immunosuppressive interaction with PD-L1. Even though PD-1 is already used as a drug target, the exact mechanism of the receptor is still a matter of debate. For instance, it is hypothesized that the signal transduction is based on an active conformation of PD-1. Results Here we present the results of the first molecular dynamics simulations of PD-1 with a complete extracellular domain with a focus on the role of the BC-loop of PD-1 upon binding PD-L1 or nivolumab. We could demonstrate that the BC-loop can form three conformations. Nivolumab binds to the BC-loop according to the conformational selection model whereas PD-L1 induces allosterically a conformational change of the BC-loop. Conclusion Due to the structural differences of the BC-loop, a signal transduction based on active conformation cannot be ruled out. These findings will have an impact on drug design and will help to refine immunotherapy blocking antibodies.

Sign in / Sign up

Export Citation Format

Share Document