Alloreactive CD8+ T cells targeting minor histocompatibility antigens (MiHA) on malignant cells of the recipient play a pivotal role in graft-versus-tumor responses observed after allogeneic stem cell transplantation and donor lymphocyte infusion (DLI). However, these MiHA-specific CD8+ T-cell responses do not result in complete eradication of tumor cells in all patients. Furthermore, CD8+ memory T cells persisting after DLI do not always efficiently expand with recurrence of the disease. Adjuvant immunotherapy using dendritic cells (DC) loaded with hematopoietic-restricted MiHA may boost antitumor CD8+ T-cell immunity without inducing graft-versus-host disease. Here, we explored the use of mRNA-electroporated DC to stimulate MiHA-specific CD8+ T-cell responses. We demonstrate that electroporation of mature DC with P2X5 mRNA encoding for hematopoietic-restricted MiHA LRH-1 results in high expression of both mRNA and protein, and has no negative effect on the mature phenotype and migratory capacity of the DC. Furthermore, these DC can efficiently stimulate LRH-1-specific CD8+ effector T cells to proliferate and produce interferon-gamma. In addition, LRH-1-specific CD8+ memory T cells that are present in patient-derived peripheral blood mononuclear cells at long periods post-DLI can be effectively activated by stimulation with P2X5 mRNA-electroporated DC to proliferate and degranulate upon target cell recognition. These results indicate that adjuvant immunotherapy using DC electroporated with mRNA encoding hematopoietic-restricted MiHA mismatched between patients and donors may enhance the graft versus tumor response induced by stem cell transplantation and DLI.

Download full-text PDF

Source
http://dx.doi.org/10.1097/CJI.0b013e3181987c22DOI Listing

Publication Analysis

Top Keywords

cd8+ t-cell
16
lrh-1-specific cd8+
12
t-cell responses
12
hematopoietic-restricted miha
12
cells
9
cd8+
8
stimulation p2x5
8
p2x5 mrna-electroporated
8
dendritic cells
8
stem cell
8

Similar Publications

Background/objectives: Common Variable Immunodeficiency Disease (CVID) and other immunodeficiencies can present in subtle and variable ways. Whether or not a genetic lesion can be identified, there are not well understood biomarkers that quantitatively describe how severe a deficiency is. Here we discuss two possible ranking systems, CD4/CD8 T cell ratios and Immune Health Grades, and how such data maybe applicable to some immunodeficiencies.

View Article and Find Full Text PDF

Background: Activin A, a noteworthy member of the TGF-β superfamily. Activin A can regulate the biological functions of various immune cells, such as macrophages, neutrophils, NK cells, etc. The purpose of this study is to investigate the regulatory effect and related mechanisms of activin A on CD8 T cells.

View Article and Find Full Text PDF

Predicting intra-abdominal candidiasis in elderly septic patients using machine learning based on lymphocyte subtyping: a prospective cohort study.

Front Pharmacol

December 2024

Department of Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.

Objective: Intra-abdominal candidiasis (IAC) is difficult to predict in elderly septic patients with intra-abdominal infection (IAI). This study aimed to develop and validate a nomogram based on lymphocyte subtyping and clinical factors for the early and rapid prediction of IAC in elderly septic patients.

Methods: A prospective cohort study of 284 consecutive elderly patients diagnosed with sepsis and IAI was performed.

View Article and Find Full Text PDF

Immunogenicity and protective efficacy of recombinant chimeric antigens based on surface proteins of .

Front Immunol

December 2024

Department of Molecular Microbiology, Institute of Microbiology, Biotechnology and Immunology, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.

Introduction: Toxoplasmosis is caused by the opportunistic, cosmopolitan protozoan is one of the most common parasitoses in the world. This parasite can pose a threat to people with immunodeficiency but also to the fetus, since the invasion can lead to miscarriages. Moreover, this parasite can contribute to economic losses in livestock farming.

View Article and Find Full Text PDF

TLS and immune cell profiling: immunomodulatory effects of immunochemotherapy on tumor microenvironment in resectable stage III NSCLC.

Front Immunol

December 2024

State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.

Background: The use of programmed death-1 (PD-1) inhibitors in the neoadjuvant setting for patients with resectable stage III NSCLC has revolutionized this field in recent years. However, there is still 40%-60% of patients do not benefit from this approach. The complex interactions between immune cell subtypes and tertiary lymphoid structures (TLSs) within the tumor microenvironment (TME) may influence prognosis and the response to immunochemotherapy.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!