scholarly journals The combination therapy with the cytotoxic T lymphocyte-associated antigen-4 and programmed death 1 antibody-induced asthma in a patient with advanced melanoma

2021 ◽  
Vol 17 (3) ◽  
pp. 808
Author(s):  
Jun Guo ◽  
Weiran Xu ◽  
Bin Lian ◽  
Chuanliang Cui
Keyword(s):  
Combination Therapy ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Advanced Melanoma ◽  
Programmed Death ◽  
Programmed Death 1

scholarly journals Cytotoxic T-Lymphocyte-Associated Antigen 4 (CTLA-4)- and Programmed Death 1 (PD-1)-Mediated Regulation of Monofunctional and Dual Functional CD4+ and CD8+ T-Cell Responses in a Chronic Helminth Infection

2019 ◽  
Vol 87 (12) ◽  
Author(s):  
Anuradha Rajamanickam ◽  
Saravanan Munisankar ◽  
Chandrakumar Dolla ◽  
Thomas B. Nutman ◽  
Subash Babu
Keyword(s):  
T Cell ◽  
T Lymphocyte ◽  
Helminth Infection ◽  
Cytotoxic T Lymphocyte ◽  
T Cell Responses ◽  
Content Type ◽  
Cell Responses ◽  
Dual Functional ◽  
Programmed Death ◽  
Programmed Death 1

ABSTRACT Chronic helminth infections are known to be associated with the modulation of antigen-specific T-cell responses. Strongyloides stercoralis infection is characterized by the downmodulation of antigen-specific Th1 and Th17 responses and the upregulation of Th2 and Th9 responses. Immune homeostasis is partially maintained by negative regulators of T-cell activation, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1), which dampen effector responses during chronic infections. However, their roles in S. stercoralis infection are yet to be defined. Therefore, we sought to determine the role of CTLA-4 and PD-1 in regulating CD4+ and CD8+ T-cell responses and examined the frequencies of monofunctional and dual functional Th1/T cytotoxic type 1 (Tc1), Th17/Tc17, Th2/Tc2, and Th9/Tc9 cells in S. stercoralis infection in 15 infected individuals stimulated with parasite antigen following CTLA-4 or PD-1 blockade. Our data reveal that CTLA-4 or PD-1 blockade results in significantly enhanced frequencies of monofunctional and dual functional Th1/Tc1 and Th17/Tc17 cells and, in contrast, diminishes the frequencies of monofunctional and dual functional Th2/Tc2 and Th9/Tc9 cells with parasite antigen stimulation in whole-blood cultures. Thus, we demonstrate that CTLA-4 and PD-1 limit the induction of particular T-cell subsets in S. stercoralis infection, which suggests the importance of CTLA-4 and PD-1 in immune modulation in a chronic helminth infection.

Interactions between programmed death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) gene polymorphisms in type 1 diabetes

2009 ◽  
Vol 83 (3) ◽  
pp. 289-294 ◽  
Author(s):  
Scherezade Momin ◽  
Sylvia Flores ◽  
Bárbara Angel B ◽  
Ethel Codner D ◽  
Elena Carrasco P ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
T Lymphocyte ◽  
Gene Polymorphisms ◽  
Cytotoxic T Lymphocyte ◽  
Lymphocyte Antigen ◽  
Programmed Death ◽  
Programmed Death 1

scholarly journals Immune checkpoints programmed death 1 ligand 1 and cytotoxic T lymphocyte associated molecule 4 in gastric adenocarcinoma

2015 ◽  
Vol 5 (5) ◽  
pp. e1100789 ◽  
Author(s):  
Hans A. Schlößer ◽  
Uta Drebber ◽  
Michael Kloth ◽  
Martin Thelen ◽  
Sacha I. Rothschild ◽  
...  
Keyword(s):  
Gastric Adenocarcinoma ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Immune Checkpoints ◽  
Programmed Death ◽  
Programmed Death 1

scholarly journals P12.06 Clinicopathological evaluation of PD-L1 expression and cytotoxic T-lymphocyte infiltrates across intracranial molecular subgroups of ependymomas

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii60-iii60
Author(s):  
A Sharma
Keyword(s):  
Protein Expression ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Molecular Subgroups ◽  
Chromosome 1Q ◽  
Not Otherwise Specified ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Grade Ii ◽  
L1 Protein

Abstract BACKGROUND Immune check-point blockade targeting programmed cell death ligand-1 (PD-L1)/programmed death-1 (PD-1) axis has created paradigm shift in the treatment of advanced cancer. The prognosis of the ‘ST-RELA’ and ‘PF-A’ molecular subgroups of ependymomas (EPN) remains poor. This study aims to understand the potential candidature of EPNs for ICB. MATERIAL AND METHODS All supratentorial (ST) Grade II/III EPNs were classified into ST-RELA, ST-YAP and ST-not otherwise specified (NOS), based on L1CAM protein expression and/or presence of RELA/YAP1 fusion transcripts by RT-PCR. All posterior fossa (PF) BEPNs were classified into PF-A and PF-B based on H3K27me3 protein expression and chromosome 1q gain. Immunohistochemistry for PD-L1 (SP263, Ventana) and CD8 was performed. RelA protein enrichment at PDL1 promoter site was analysed by chromatin immunoprecipitation-qPCR (ChIP-qPCR) in three ST-RELA samples. RESULTS A total of 83 intracranial EPNs were included as follows: ST-RELA (n=32), ST-YAP (n=1), ST-NOS (n=11), ST-subependymoma (n=1), PF-A (n=25) and PF-B (n=13). Median tumor infiltrating CD8+ cytotoxic T-lymphocyte (CTL) density was 6/mm2, and was higher in ST EPNs (median 10/mm2) as compared to PF EPNs (median 3/mm2). PD-L1 protein expression in ≥1% tumor cells was noted in 17/83 (20%) of all EPNs, including 12/32 (37%) of ST-RELA and rare ST-NOS (2/11), PF-A (2/25) and PF-B (1/13) tumors. Twelve intracranial EPNs (14%, 12/83) showed high CTL density and concurrent PD-L1 positivity, of which majority (83%, 10/12) were ST-RELA EPNs. Enrichment of RelA protein was seen at PD-L1 promoter. CONCLUSION Increased CTL densities and upregulation of PD-L1 in ST-RELA ependymomas suggests potential candidature for immunotherapy.

scholarly journals Pembrolizumab-associated autoimmune haemolytic anaemia

2019 ◽  
Vol 12 (10) ◽  
pp. e229064 ◽  
Author(s):  
Philippa Johnstone ◽  
Omar Khan
Keyword(s):  
Haemolytic Anaemia ◽  
T Lymphocyte ◽  
Rare Case ◽  
Clinical Case ◽  
Cytotoxic T Lymphocyte ◽  
Autoimmune Haemolytic Anaemia ◽  
High Dose ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Programmed Death 1

Treatment paradigms have recently changed with the introduction of immunotherapy; autoimmune toxicities that can arise are frequently very different from the more familiar chemotherapy toxicities. We present a clinical case of autoimmune haemolytic anaemia (AIHA) secondary to pembrolizumab occurring in a 73-year-old male patient being treated for lung adenocarcinoma, who had received 13 cycles of pembrolizumab. Treatment was immediately stopped and he was treated with high dose steroids to which he responded both clinically and biochemically. There have been prior reports of immunotherapy-associated AIHA with the use of cytotoxic T-lymphocyte-associated antigen-4 inhibitors, such as ipilimumab, but very few reports of programmed death-1 (PD-1)/programmed death-ligand 1 (PDL-1) inhibitor associated AIHA. We highlight a rare case of AIHA as an adverse effect of pembrolizumab, a PD-1 inhibitor. Although unusual, it is important to be vigilant for haematological immune-related adverse events.

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