4.7 Article

Follicular lymphoma B cells induce the conversion of conventional CD4+ T cells to T-regulatory cells

期刊

INTERNATIONAL JOURNAL OF CANCER
卷 124, 期 1, 页码 239-244

出版社

WILEY
DOI: 10.1002/ijc.23881

关键词

tumor microenvironment; immune escape

类别

资金

  1. National Institute of Health
  2. Doris Duke Charitable Foundation
  3. Lymphoma Research Foundation
  4. American Society of Clinical Oncology Young Investigator
  5. Deutsche Krebshilfe, Germany

向作者/读者索取更多资源

There has been accumulating evidence that CD4(+)CD25(+) FoxP3 expressing regulatory T cells (Treg) are highly concentrated in tumors, thereby fostering an immune-privileged microenvironment. Some studies have shown that T-cell receptor (TCR) stimulation can convert conventional T cells into Treg. Follicular lymphoma (FL) It cells can enhance this Treg conversion. We investigated whether FL tumor B cells, as opposed to normal B cells, are unique in their ability to convert effector T cells into Treg. We found that tumor B cells alone, without artificial TCR stimulation, could induce conventional T cells to express FoxP3 and to acquire regulatory function. In contrast to their malignant counterpart, normal It cells did not induce Treg conversion. Treg conversion was independent of the T cell background, as T cells isolated from FL or normal peripheral blood were equally susceptible to being converted by tumor B cells. Our study provides evidence for a tumor-specific mechanism by which FL tumor cells promote immune escape through the induction of Treg. (C) 2008 Wiley-Liss, Inc.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

Article Biochemistry & Molecular Biology

Fingolimod-Conjugated Charge-Altering Releasable Transporters Efficiently and Specifically Deliver mRNA to Lymphocytes In Vivo and In Vitro

Stefano Testa, Ole A. W. Haabeth, Timothy R. Blake, Trevor J. Del Castillo, Debra K. Czerwinski, Ranjani Rajapaksa, Paul A. Wender, Robert M. Waymouth, Ronald Levy

Summary: Charge-altering releasable transporters (CARTs) containing fingolimod were synthesized to enhance mRNA delivery and expression in lymphocytes through ligand-receptor interaction. The fingolimod-conjugated CARTs showed superior transfection of activated T and B lymphocytes in vitro and increased mRNA delivery to specific cell populations in the spleen in vivo.

BIOMACROMOLECULES (2022)

Article Oncology

Rituximab Chimeric Anti-CD20 Monoclonal Antibody Therapy for Relapsed Indolent Lymphoma: Half of Patients Respond to a Four-Dose Treatment Program

Peter McLaughlin, Antonio J. Grillo-Lopez, Brain K. Link, Ronald Levy, Myron S. Czuczman, Michael E. Williams, Meyer R. Heyman, Isabelle Bence-Bruckler, Christine A. White, Fernando Cabanillas, Vinay Jain, Anthony D. Ho, John Lister, Key Wey, David Shen, Brain K. Dallaire

Summary: In this study, the chimeric anti-CD20 antibody IDEC-C2B8 was used to treat patients with relapsed low grade or follicular lymphoma. The response rate was 48%, comparable to single-agent cyto-toxic chemotherapy. Further research is needed to determine the efficacy of this agent and its potential use in combination with standard chemotherapy.

JOURNAL OF CLINICAL ONCOLOGY (2023)

Article Biochemical Research Methods

Lysine-Derived Charge-Altering Releasable Transporters: Targeted Delivery of mRNA and siRNA to the Lungs

Timothy R. Blake, Ole A. W. Haabeth, Adrienne Sallets, Rebecca L. McClellan, Trevor J. Del Castillo, Jose G. Vilches-Moure, Wilson C. Ho, Paul A. Wender, Ronald Levy, Robert M. Waymouth

Summary: Targeted delivery of nucleic acid therapeutics to the lungs shows promise for treating pulmonary diseases. New lysine-derived CART-mRNA complexes (K-CARTs/mRNA) demonstrate selective protein expression in the lungs without additives or targeting ligands. The ability to direct protein expression selectively in the spleen or lungs by simple changes to the CART structure opens new opportunities in research and gene therapy.

BIOCONJUGATE CHEMISTRY (2023)

Review Hematology

Pathophysiology of gastrointestinal acute graft-versus-host disease and the potential role of glucagon-like peptide 2

Robert Zeiser, Yi-Bin Chen, Nader N. Youssef, Francis Ayuk

Summary: Acute graft-versus-host disease (aGVHD) is a severe complication after allogeneic haematopoietic cell transplantation, with gastrointestinal (GI) tract involvement (GI aGVHD) being a major cause of morbidity and mortality. Despite systemic steroids being the standard treatment for aGVHD, around 50% of patients do not respond to steroids, leading to poor outcomes. This review discusses the role of glucagon-like peptide 2 (GLP-2) in protecting and maintaining GI epithelial cells, as well as the potential use of the GLP-2 analogue apraglutide as an adjunctive treatment for GI aGVHD.

BRITISH JOURNAL OF HAEMATOLOGY (2023)

Article Oncology

Novel Approaches to the Treatment of Chronic Graft-Versus-Host Disease

Robert Zeiser

Summary: This study summarizes the treatment approach for chronic graft-versus-host disease (cGVHD) and finds that adding ibrutinib to first-line therapy is not recommended. Currently, glucocorticoid monotherapy remains the standard treatment for cGVHD.

JOURNAL OF CLINICAL ONCOLOGY (2023)

Article Multidisciplinary Sciences

The molecular mechanism of CD81 antibody inhibition of metastasis

Niroz Abu-Saleh, Chiung-Chi Kuo, Wei Jiang, Ronald Levy, Shoshana Levy

Summary: Metastases are decreased in CD81KO mice. Moreover, a specific anti-CD81 antibody, 5A6, can inhibit metastasis in vivo and invasion and migration in vitro. Removing cholesterol or the intracellular domains of CD81 doesn't affect 5A6's inhibitory effect. The uniqueness of 5A6 is attributed to its recognition of a specific epitope on CD81's large extracellular loop. Finally, several CD81 membrane-associated partners, such as integrins and transferrin receptors, may contribute to the antimetastatic attributes of 5A6.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2023)

Editorial Material Clinical Neurology

Immune checkpoint inhibitor induced neurocognitive deficits in patients

Robert Zeiser, Marco Prinz

Summary: This scientific commentary discusses the neurological effects of immune checkpoint inhibitor-related neurotoxicity, based on the study by Farina et al.

BRAIN COMMUNICATIONS (2023)

Article Biophysics

A novel approach to visualize clinical benefit of therapies for chronic graft versus host disease (cGvHD): the probability of being in response (PBR) applied to the REACH3 study

Norbert Hollaender, Ekkehard Glimm, Jennifer Gauvin, Tommaso Stefanelli, Robert Zeiser

Summary: Overall response rate (ORR) and best overall response rate (BOR) are commonly used as key endpoints to evaluate the efficacy of treatments for chronic graft versus host disease (cGvHD). This study introduced the probability of being in response (PBR) as a novel measure and demonstrated that Ruxolitinib showed better response rates and longer response duration compared to the best available therapy (BAT). PBR is a clinically interpretable measurement and can be a useful endpoint for assessing cGvHD treatments.

BONE MARROW TRANSPLANTATION (2023)

Review Hematology

Chimeric antigen receptor T cells for acute myeloid leukemia

Viktor Fetsch, Robert Zeiser

Summary: The use of CAR T cells has greatly impacted the treatment of B-cell malignancies, but it has not yet been widely adopted for myeloid malignancies like AML or MPNs. This article discusses the challenges in using CAR T cells for myeloid malignancies and presents novel approaches to enhance their efficacy and reduce toxicity.

EUROPEAN JOURNAL OF HAEMATOLOGY (2023)

Article Hematology

Identification of clinical factors impacting outcome in patients undergoing autologous hematopoietic cell transplantation after BEAM and TEAM conditioning

Radu-Florian Gherman, Sophie Ewald, Gabriele Ihorst, Tim Strussmann, Robert Zeiser, Ralph Waesch, Hartmut Bertz, Daiana Stolz, Justus Duyster, Juergen Finke, Reinhard Marks, Monika Engelhardt, Jesus Duque-Afonso

Summary: This study retrospectively analyzed the outcomes of 396 patients undergoing autologous hematopoietic stem cell transplantation with BEAM or TEAM conditioning protocols. The results showed that BEAM conditioning was associated with worse survival outcomes in patients with impaired pulmonary function, while PD before transplantation was the only significant factor in patients treated with TEAM.

EUROPEAN JOURNAL OF HAEMATOLOGY (2023)

Review Immunology

Novel therapies for graft versus host disease with a focus on cell therapies

Robert Zeiser, Olle Ringden, Behnam Sadeghi, Gil Gonen-Yaacovi, Oscar G. Segurado

Summary: Graft versus host disease (GVHD) is a common clinical complication that can occur at any period post allogeneic hematopoietic stem cell transplantation. There is currently no consensus on the management of steroid-refractory acute GVHD and the prognosis for these patients remains poor. Recent advancements in cell therapies, particularly the use of decidua stromal cells (DSCs), have shown promising results in the treatment of acute GVHD.

FRONTIERS IN IMMUNOLOGY (2023)

Article Oncology

Functional Characterization of Transforming Growth Factor-β Signaling in Dasatinib Resistance and Pre-BCR+ Acute Lymphoblastic Leukemia

Gila Mostufi-Zadeh-Haghighi, Pia Veratti, Kyra Zodel, Gabriele Greve, Miguel Waterhouse, Robert Zeiser, Michael L. Cleary, Michael Luebbert, Jesus Duque-Afonso

Summary: This study focused on the characterization of the TGF beta signaling pathway in B-acute lymphoblastic leukemia (ALL) and resistance to the multi-kinase inhibitor dasatinib. The results showed that TGF beta signaling negatively regulates cell growth in B-cell precursor-ALL and in dasatinib-resistant ALL cells. The upregulation of the TGF beta pathway was identified in dasatinib-resistant pre-BCR+/E2A-PBX1(+) ALL cells, and dasatinib partially blocked TGF beta-induced SMAD3 phosphorylation in B-cell precursor ALL cell lines and dasatinib-resistant pre-BCR+/E2A-PBX1(+) ALL cells.

CANCERS (2023)

Article Biochemistry & Molecular Biology

Single-cell multi-gene identification of somatic mutations and gene rearrangements in cancer

Susan M. Grimes, Heon Seok Kim, Sharmili Roy, Anuja Sathe, Carlos Ayala, Xiangqi Bai, Alison F. Almeda-Notestine, Sarah Haebe, Tanaya Shree, Ronald Levy, Billy T. Lau, Hanlee P. Ji

Summary: In this study, a single-cell method was developed to determine the genotypes of somatic alterations in coding regions of messenger RNAs and integrate these transcript-based variants with their corresponding cell transcriptomes. Nanopore adaptive sampling on single-cell complementary DNA libraries was used to validate coding variants in target gene transcripts, and short-read sequencing was used to characterize the cell types harboring the mutations. CRISPR edits for 16 targets were identified using a cancer cell line, and known variants in the cell line were validated using a 352-gene panel. Variants in primary cancer samples were validated using target gene panels ranging from 161 to 529 genes. A gene rearrangement was also identified in one patient, with the rearrangement occurring in two distinct tumor sites.

NAR CANCER (2023)

Article Oncology

Long-term follow-up of patients with acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplantation after primary induction failure

Miriam Mozaffari Jovein, Gabriele Ihorst, Jesus Duque-Afonso, Ralph Waesch, Hartmut Bertz, Claudia Wehr, Justus Duyster, Robert Zeiser, Juergen Finke, Florian Scherer

Summary: This study evaluated the long-term outcomes of 220 AML patients after primary induction failure (PIF) who underwent allogeneic hematopoietic stem cell transplantation (HCT). The results showed that immediate allogeneic HCT after PIF provides long-term survival and cure in a high-risk population.

BLOOD CANCER JOURNAL (2023)

Article Hematology

Novel developments in the prophylaxis and treatment of acute GVHD

Omer Jamy, Robert Zeiser, Yi-Bin Chen

Summary: Acute graft-versus-host disease (aGVHD) is a severe complication after allogeneic hematopoietic cell transplant, and the traditional prophylactic and treatment strategies have been reshaped by the approval of new drugs and the emergence of new therapies. Ongoing clinical trials and future goals in this field are discussed, along with the limitations of current trial designs and endpoints.
Article Oncology

Anal cancer screening results from 18-to-34-year-old men who have sex with men living with HIV

Yuxin Liu, Swati Bhardwaj, Keith Sigel, John Winters, Joseph Terlizzi, Michael M. Gaisa

Summary: This study investigated the prevalence and severity of anal HPV disease among MSM LWH under the age of 35, finding a high prevalence of HPV infection and precancer but no cases of invasive anal cancer. This supports the adoption of age-based anal cancer screening for this population.

INTERNATIONAL JOURNAL OF CANCER (2024)