Caffeine-enhanced anti-tumor immune response through decreased expression of PD1 on infiltrated cytotoxic T lymphocytes

2019 ◽  
Vol 859 ◽  
pp. 172538 ◽  
Author(s):  
Gullanki Naga Venkata Charan Tej ◽  
Kaushik Neogi ◽  
Sumit Singh Verma ◽  
Subash Chandra Gupta ◽  
Prasanta Kumar Nayak
Keyword(s):  
Immune Response ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes

scholarly journals Combining PARP inhibition, radiation, and immunotherapy: A possible strategy to improve the treatment of cancer?

2018 ◽  
Vol 19 (12) ◽  
pp. 3793 ◽  
Author(s):  
Mathieu Césaire ◽  
Juliette Thariat ◽  
Serge M. Candéias ◽  
Dinu Stefan ◽  
Yannick Saintigny ◽  
...  
Keyword(s):  
Immune Response ◽  
Radiation Therapy ◽  
T Lymphocytes ◽  
Ionizing Radiation ◽  
Cytotoxic T Lymphocytes ◽  
Tumor Antigens ◽  
Checkpoint Inhibitors ◽  
Parp Inhibitors ◽  
Antitumor Immune Response ◽  
Parp Inhibition

Immunotherapy has revolutionized the practice of oncology, improving survival in certain groups of patients with cancer. Immunotherapy can synergize with radiation therapy, increase locoregional control, and have abscopal effects. Combining it with other treatments, such as targeted therapies, is a promising means of improving the efficacy of immunotherapy. Because the value of immunotherapy is amplified with the expression of tumor antigens, coupling poly(ADP-ribose) polymerase (PARP) inhibitors and immunotherapy might be a promising treatment for cancer. Further, PARP inhibitors (PARPis) are being combined with radiation therapy to inhibit DNA repair functions, thus enhancing the effects of radiation; this association might interact with the antitumor immune response. Cytotoxic T lymphocytes are central to the antitumor immune response. PARP inhibitors and ionizing radiation can enhance the infiltration of cytotoxic T lymphocytes into the tumor bed, but they can also enhance PD-1/PDL-1 expression. Thus, the addition of immune checkpoint inhibitors with PARP inhibitors and/or ionizing radiation could counterbalance such immunosuppressive effects. With the present review article, we proposed to evaluate some of these associated therapies, and we explored the biological mechanisms and medical benefits of the potential combination of radiation therapy, immunotherapy, and PARP inhibitors.

scholarly journals Development of a Bioconjugate Platform for Modifying the Immune Response of Autoreactive Cytotoxic T Lymphocytes Involved in Type 1 Diabetes

2019 ◽  
Vol 30 (7) ◽  
pp. 2049-2059 ◽  
Author(s):  
Neha Nandedkar-Kulkarni ◽  
Abhishek R. Vartak ◽  
Steven J. Sucheck ◽  
Katherine A. Wall ◽  
Anthony Quinn ◽  
...  
Keyword(s):  
Immune Response ◽  
Type 1 Diabetes ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes

scholarly journals Low Frequency of Cytotoxic T Lymphocytes against the Novel HLA-A*0201-Restricted JC Virus Epitope VP1p36 in Patients with Proven or Possible Progressive Multifocal Leukoencephalopathy

2003 ◽  
Vol 77 (22) ◽  
pp. 11918-11926 ◽  
Author(s):  
Renaud A. Du Pasquier ◽  
Marcelo J. Kuroda ◽  
Joern E. Schmitz ◽  
Yue Zheng ◽  
Kristi Martin ◽  
...  
Keyword(s):  
Immune Response ◽  
T Lymphocytes ◽  
Progressive Multifocal Leukoencephalopathy ◽  
Cytotoxic T Lymphocytes ◽  
Peripheral Blood ◽  
Cellular Immune Response ◽  
Jc Virus ◽  
The Novel ◽  
Tetramer Staining ◽  
Cellular Immune

ABSTRACT JC virus (JCV)-specific cytotoxic T lymphocytes (CTL) in peripheral blood are associated with a favorable outcome in patients with progressive multifocal leukoencephalopathy (PML). However, the frequency of these cells in the peripheral blood mononuclear cells (PBMC) of PML patients is unknown. To develop a highly sensitive assay for detecting the cellular immune response against this virus, we performed a CTL epitope mapping study of JCV VP1 major capsid protein by using overlapping peptides. A novel HLA-A*0201-restricted epitope, the VP1p36 peptide SITEVECFL, was characterized. The cellular immune response against JCV was assessed in 32 study subjects. By combining the results of the 51Cr release assay on pooled peptides and staining with the HLA-A*0201/JCV VP1p36 tetramer, VP1-specific CTL were detected in 10 of 11 PML survivors (91%) versus only 1 of 11 PML progressors (9%, P = 0.0003). VP1-specific CTL were also detected in two of two patients recently diagnosed with PML and in four of four human immunodeficiency virus-positive patients with possible PML. The frequency of CTL specific for the novel VP1p36 and the previously described VP1p100 epitopes was determined. In two patients, the frequency of CTL specific for the VP1p36 or VP1p100 epitopes, as determined by fresh blood tetramer staining (FBTS), ranged from 1/6,000 to 1/24,000 PBMC. A CTL sorting technique combining tetramer staining and selection with immunomagnetic beads allowed the detection of epitope-specific CTL in two cases that were determined to be negative by FBTS. The phenotype of these CTL in vivo was consistent with activated memory cells. These data suggest that, although present in low numbers, JCV-specific CTL may be of central importance in the containment of JCV spread in immunosuppressed individuals.

scholarly journals DNA Immunization with Trypanosoma cruzi HSP70 Fused to the KMP11 Protein Elicits a Cytotoxic and Humoral Immune Response against the Antigen and Leads to Protection

2001 ◽  
Vol 69 (10) ◽  
pp. 6558-6563 ◽  
Author(s):  
Lourdes Planelles ◽  
M. Carmen Thomas ◽  
Carlos Alonso ◽  
Manuel C. López
Keyword(s):  
Immune Response ◽  
T Lymphocytes ◽  
Trypanosoma Cruzi ◽  
Cytotoxic T Lymphocytes ◽  
Humoral Immune Response ◽  
Chimeric Gene ◽  
Dna Immunization ◽  
Humoral Immune ◽  
Parasite Challenge

ABSTRACT Murine immunization with Trypanosoma cruzi KMP11-HSP70fused genes but not the KMP11 gene alone elicited both an immunoglobulin G2a long-lasting humoral immune response against KMP11 protein and activation of CD8+ cytotoxic T lymphocytes specific for two KMP11 peptides containing A2 motifs. Moreover, protection against the parasite challenge was observed after immunization with the chimeric gene.

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