The immunoregulatory protein CD200 as a potentially lucrative yet elusive target for cancer therapy

Shao, Anqi; Owens, David M.

doi:10.18632/oncotarget.28354

Cited by 14 publications

(8 citation statements)

References 72 publications

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“…CD200 activation stimulates the differentiation of T cells to the Treg subset and modulates cytokine environment from a Th1 to a Th2 pattern [ 19 – 28 ]. CD200 is also an immunoregulatory cell surface ligand with proven pro-tumorigenic credentials via its ability to suppress CD200 receptor (CD200R)-expressing antitumor immune function [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Leukocytes, B and T Lymphocytes, and expression of CD200 and CD23 on B lymphocytes in Patients with Atopic Dermatitis on Dupilumab Therapy—Pilot Study

Čelakovská

Čermáková

Boudková

et al. 2023

Dermatol Ther (Heidelb)

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Background There are a lot of studies that describe the change in quantity of T cells in patients with atopic dermatitis (AD) compared with healthy subjects. Other components of lymphocytes such as B cells are not examined as well as T cells. Objective We focus on immunophenotyping of B cells with their subsets (memory, naïve, switched, non-switched) and the expression of CD23 and CD200 markers in patients with AD with and without dupilumab therapy. We also evaluate the count of leukocytes and their subsets, T lymphocytes (CD4 + , CD8 + ), natural killer (NK) cells, and T regulatory cells. Methods A total of 45 patients suffering from AD were examined: 32 patients without dupilumab treatment (10 men, 22 women, average age 35 years), 13 patients with dupilumab treatment (7 men, 6 women, average age 43.4 years), and 30 subjects as a control group (10 men, 20 women, average age 44.7 years). Immunophenotype was examined by flow cytometry in which monoclonal antibodies with fluorescent molecules were used. We compared the absolute and relative count of leukocytes and their subsets, T lymphocytes (CD4 + , CD8 + ), NK cells, T regulatory cells, absolute and relative count of B lymphocytes (memory, naïve, non-switched, switched, transient), and expression of CD23 and CD200 activation markers on B cells and on their subsets in patients with AD and control group. For statistical analysis we used nonparametric Kruskal–Wallis one-factor analysis of variance with post hoc by Dunn’s test with Bonferroni modification of significance level. Results In patients with AD with and without dupilumab therapy we confirmed the significantly higher count of neutrophils, monocytes, and eosinophils; there was no difference in absolute count of B cells, NK cells and transitional B cells compared with control subjects. We confirmed higher expression of activation marker CD23 on total, memory, naïve, non-switched, and switched B lymphocytes and higher expression of CD200 on total B lymphocytes in both groups of patients with AD compared with controls. In patients without dupilumab therapy we confirmed significantly higher count of relative monocytes, relative eosinophils, and higher expression of CD200 on memory, naïve, and non-switched B lymphocytes compared with controls. In patients with dupilumab therapy we confirmed significantly higher expression of CD200 on switched B lymphocytes, higher count of relative CD4 + T lymphocytes, and lower count of absolute CD8 + T lymphocytes compared with controls. Conclusion This pilot study shows higher expression of CD23 on B lymphocytes and on their subsets in patients with AD with and without dupilumab therapy. The higher expression of CD200 on switched B lymphocytes is confirmed only in patients with AD with ...

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Section: Introductionmentioning

confidence: 99%

Evaluation of Leukocytes, B and T Lymphocytes, and expression of CD200 and CD23 on B lymphocytes in Patients with Atopic Dermatitis on Dupilumab Therapy—Pilot Study

Čelakovská

Čermáková

Boudková

et al. 2023

Dermatol Ther (Heidelb)

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“…Conversely, a more promising approach for Breg depletion therapy involves exploring alternative Breg-specific markers. For example, CD200 is a type I membrane-associated glycoprotein related to an immunoregulatory signaling pathway, which is detectable across multiple haemalogic malignancies and solid cancers ( 233 ). In HPV + HNSCC patients, CD200 + expressing Breg cells were identified ( 133 ).…”

Section: Targeting Til-b Cells For Immunotherapymentioning

confidence: 99%

Exploring the dual role of B cells in solid tumors: implications for head and neck squamous cell carcinoma

Bao,

Betzler,

Hess

et al. 2023

Front. Immunol.

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In the tumor milieu of head and neck squamous cell carcinoma (HNSCC), distinct B cell subpopulations are present, which exert either pro- or anti-tumor activities. Multiple factors, including hypoxia, cytokines, interactions with tumor cells, and other immune infiltrating lymphocytes (TILs), alter the equilibrium between the dual roles of B cells leading to cancerogenesis. Certain B cell subsets in the tumor microenvironment (TME) exhibit immunosuppressive function. These cells are known as regulatory B (Breg) cells. Breg cells suppress immune responses by secreting a series of immunosuppressive cytokines, including IL-10, IL-35, TGF-β, granzyme B, and adenosine or dampen effector TILs by intercellular contacts. Multiple Breg phenotypes have been discovered in human and mouse cancer models. However, when compartmentalized within a tertiary lymphoid structure (TLS), B cells predominantly play anti-tumor effects. A mature TLS contains a CD20+ B cell zone with several important types of B cells, including germinal-center like B cells, antibody-secreting plasma cells, and memory B cells. They kill tumor cells via antibody-dependent cytotoxicity and phagocytosis, and local complement activation effects. TLSs are also privileged sites for local T and B cell coordination and activation. Nonetheless, in some cases, TLSs may serve as a niche for hidden tumor cells and indicate a bad prognosis. Thus, TIL-B cells exhibit bidirectional immune-modulatory activity and are responsive to a variety of immunotherapies. In this review, we discuss the functional distinctions between immunosuppressive Breg cells and immunogenic effector B cells that mature within TLSs with the focus on tumors of HNSCC patients. Additionally, we review contemporary immunotherapies that aim to target TIL-B cells. For the development of innovative therapeutic approaches to complement T-cell-based immunotherapy, a full understanding of either effector B cells or Breg cells is necessary.

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“…Recently, Shao A. et al. ( 40 ) reported a review about the CD200 expression and function in the tumor microenvironment as well as alternative strategies for potential neutralization of CD200 in human cancers, indicating that a probable explanation for the observed shortcomings in the samalizumab phase I trial could be the alternative mechanisms for the CD200 pro-tumorigenic role, beyond direct suppression of anti-tumor T cell responses, such as engagement of the CD200-CD200R axis, transcriptional mechanisms related to the cleaved cytoplasmic tail and ectodomain shedding. Consistently with these observations, combined blocking other immune checkpoint molecules such as CTLA-4 or PD-1 in addition to CD200 blockade could be an option to synergistically enhance antitumor activity and improve outcomes.…”

Section: Discussionmentioning

confidence: 99%

CD200 genotype is associated with clinical outcome of patients with multiple myeloma

Gonzalez-Montes,

Osca-Gelis,

Rodriguez-Romanos

et al. 2024

Front. Immunol.

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Immune dysfunction in patients with MM affects both the innate and adaptive immune system. Molecules involved in the immune response pathways are essential to determine the ability of cancer cells to escape from the immune system surveillance. However, few data are available concerning the role of immune checkpoint molecules in predicting the myeloma control and immunological scape as mechanism of disease progression. We retrospectively analyzed the clinical impact of the CD200 genotype (rs1131199 and rs2272022) in 291 patients with newly diagnosed MM. Patients with a CD200 rs1131199 GG genotype showed a median overall survival (OS) significantly lower than those with CC+CG genotype (67.8 months versus 94.4 months respectively; p: 0.022) maintaining significance in the multivariate analysis. This effect was specially detected in patients not receiving an autologous stem cell transplant (auto-SCT) (p < 0.001). In these patients the rs1131199 GG genotype negatively influenced in the mortality not related with the progression of MM (p: 0.02) mainly due to infections events.

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The immunoregulatory protein CD200 as a potentially lucrative yet elusive target for cancer therapy

Cited by 14 publications

References 72 publications

Evaluation of Leukocytes, B and T Lymphocytes, and expression of CD200 and CD23 on B lymphocytes in Patients with Atopic Dermatitis on Dupilumab Therapy—Pilot Study

Evaluation of Leukocytes, B and T Lymphocytes, and expression of CD200 and CD23 on B lymphocytes in Patients with Atopic Dermatitis on Dupilumab Therapy—Pilot Study

Exploring the dual role of B cells in solid tumors: implications for head and neck squamous cell carcinoma

CD200 genotype is associated with clinical outcome of patients with multiple myeloma

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