The role of follicular T helper cells in patients with malignant lymphoid disease

Zhou, Dongming; Xu, Yan-Xia; Zhang, Liying; Sun, Yu; Wang, Ziyan; Yuan, Yeqing; Fu, Jinxiang

doi:10.1080/10245332.2017.1300623

Cited by 13 publications

(13 citation statements)

References 29 publications

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“…In the MM patient, a clear subset of CD4 + T cells expressed ICOS, which is a mediator and regulator of helper T cell immunity and effector T cell differentiation (55), and several cell populations, including MM cells, MDSCs, and monocytes, provide its ligand, ICOSL, for them. In keeping with this mechanism, a previous study has reported that MM patients present a higher percentage of ICOS + cells in follicular helper T cells than healthy controls (56). In an in vitro experiment, ICOS/ICOSL blockade significantly inhibited the generation of MM cell-induced T Reg (CD4 + CD25 + FoxP3 + ) cells (57), and lenalidomide, a clinically verified anti-MM immunomodulatory drug, downregulated ICOSL expression in MM cells (58) and enhanced PD-1/PD-L1 blockade-induced immune response in MM patients (59), underscoring ICOS/ICOSL blockade as a possible anti-MM immunotherapeutic sponsor and enhancer.…”

Section: Discussionmentioning

confidence: 68%

Exploration of the personalized immune checkpoint atlas of plasma cell dyscrasias patients using high‑dimensional single‑cell analysis

Zheng

Zhang

et al. 2020

Oncol Rep

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Immune checkpoint blockade endows patients with unparalleled success in conquering cancer. Unfortunately, inter-individual heterogeneity causes failure in controlling tumors in many patients. Emerging mass cytometry technology is capable of revealing a multiscale onco-immune landscape that improves the efficacy of cancer immunotherapy. We introduced mass cytometry to determine the personalized immune checkpoint status in bone marrow and peripheral blood samples from 3 patients with multiple myeloma, amyloid light-chain amyloidosis, and solitary bone plasmacytoma and 1 non-hematologic malignancy patient. The expression of 18 immune regulatory receptors and ligands on 17 defined cell populations was simultaneously examined. By single-cell analyses, we identified the T cell clusters that serve as immunosuppressive signal source and revealed integrated immune checkpoint axes of individuals, thereby providing multiple potential immunotherapeutic targets, including programmed cell death protein 1 (PD-1), inducible co-stimulator (ICOS), and cluster of differentiation 28 (CD28), for each patient. Distinguishing the cell populations that function as providers and receivers of the immune checkpoint signals demonstrated a distinct cross-interaction network of immunomodulatory signals in individuals. These in-depth personalized data demonstrate mass cytometry as a powerful innovation to discover the systematical immune status in the primary and peripheral tumor microenvironment.

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Section: Discussionmentioning

confidence: 68%

Exploration of the personalized immune checkpoint atlas of plasma cell dyscrasias patients using high‑dimensional single‑cell analysis

Zheng

Zhang

et al. 2020

Oncol Rep

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“…ICOSL was also expressed by most of MM cells, and its receptor ICOS was increasingly detected in 20–40% of CD4 or CD8 T cells of MM patients. Being in line with this mechanism, a higher percentage of ICOS + cells in follicular helper T cells has been found in MM patients than healthy controls 53 . The ICOS/ICOSL signal can mediate helper T‐cell immunity and regulate effector T‐cell differentiation 54 .…”

Section: Discussionmentioning

confidence: 81%

Identification of the immune checkpoint signature of multiple myeloma using mass cytometry‐based single‐cell analysis

Wang

Zheng

et al. 2020

Clin & Trans Imm

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Objectives New targets or strategies are needed to increase the success of immune checkpoint‐based immunotherapy for multiple myeloma (MM). However, immune checkpoint signals in MM microenvironment have not been fully elucidated. Here, we aimed to have a broad overview of the different immune subsets and their immune checkpoint status, within the MM microenvironment, and to provide novel immunotherapeutic targets to treat MM patients. Methods We performed immune checkpoint profiling of bone marrow (BM) samples from MM patients and healthy controls using mass cytometry. With high‐dimensional single‐cell analysis of 30 immune proteins containing 10 pairs of immune checkpoint axes in 0.55 million of BM cells, an immune landscape of MM was mapped. Results We identified an abnormality of immune cell composition by demonstrating a significant increase in activated CD4 T, CD8 T, CD8+ natural killer T‐like and NK cells in MM BM. Our data suggest a correlation between MM cells and immune checkpoint phenotypes and expand the view of MM immune signatures. Specifically, several critical immune checkpoints, such as programmed cell death 1 (PD‐1)/PD ligand 2, galectin‐9/T‐cell immunoglobulin mucin‐3, and inducible T‐cell costimulator (ICOS)/ICOS ligand, on both MM and immune effector cells and a number of activated PD‐1+ CD8 T cells lacking CD28 were distinguished in MM patients. Conclusion A clear interaction between MM cells and the surrounding immune cells was established, leading to immune checkpoint dysregulation. The analysis of the immune landscape enhances our understanding of the MM immunological milieu and proposes novel targets for improving immune checkpoint blockade‐based MM immunotherapy.

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“…Indeed, a recent study has found significantly higher plasma levels of TFH cells that also strongly express ICOS, PD-1, and IL-21 at pretreatment in patients with acute lymphoblastic leukemia, multiple myeloma or NHL, compared with healthy donors [ 96 ]. Moreover, comparison of TFH cell count and ICOS, PD-1, and IL-21 expression in these three groups of patients showed that they were the highest in patients with NHL.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, comparison of TFH cell count and ICOS, PD-1, and IL-21 expression in these three groups of patients showed that they were the highest in patients with NHL. These authors also observed a negative correlation between TFH cell number and therapeutic effect, implying that TFH might have a prognostic value in the clinic [ 96 ].…”

Section: Introductionmentioning

confidence: 99%

“…These trials include the open-label CALIBRATE study (rituximab followed by belimumab for lupus nephritis) and the SYNBIoSe study (Synergetic B cell Immodulation in systemic lupus erythematosus). Moreover, a very recent study on the dynamic changes of peripheral TFH cells in patients with malignant lymphoid disease during treatment showed a negative correlation between TFH numeration, therapeutic effect and remission [ 96 ].…”

Section: Introductionmentioning

confidence: 99%

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T follicular helper cells: a potential therapeutic target in follicular lymphoma

Ochando

Braza

2017

Oncotarget

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Follicular lymphoma (FL), the most common indolent B-cell non-Hodgkin lymphoma (B-NHL), is a germinal center (GC)-derived lymphoma. The mechanisms underlying B-cell differentiation/maturation in GCs could be also involved in their malignant transformation. Moreover, the non-malignant cell composition and architecture of the tumor microenvironment can influence FL development and outcome. Here, we review recent research advances on CD4 helper T cells in FL that highlight the pivotal role of T follicular helper (TFH) cells in a complex multicellular system where they interact with B cells during GC dynamics. After describing the mechanism of FL lymphomagenesis, we discuss the emerging evidence about TFH cell enrichment and involvement in FL tumorigenesis and in B-T cell interaction, TFH regulation by T follicular regulatory cells (TFR) and its potential effect on FL. Then, we provide an overview on the flexible interplay between the different CD4 T-cell subtypes and how this may be predicted in normal and pathologic contexts, according to the cell epigenetic state. Finally, we highlight the importance of targeting TFH cells in the clinic, summarize the main outstanding questions about TFH and TFR cells in FL, and describe strategies to potentiate FL therapy by taking into account TFH cells.

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The role of follicular T helper cells in patients with malignant lymphoid disease

Abstract: Significantly increased T cell ratios were found in patients with MLD, and decreased T cells ratios could be expected in those treatment-effective patients, which could be used as the therapeutic efficacy index.

Cited by 13 publications

References 29 publications

Exploration of the personalized immune checkpoint atlas of plasma cell dyscrasias patients using high‑dimensional single‑cell analysis

Exploration of the personalized immune checkpoint atlas of plasma cell dyscrasias patients using high‑dimensional single‑cell analysis

Identification of the immune checkpoint signature of multiple myeloma using mass cytometry‐based single‐cell analysis

T follicular helper cells: a potential therapeutic target in follicular lymphoma

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