CCR7 in Blood Cancers – Review of Its Pathophysiological Roles and the Potential as a Therapeutic Target

Cuesta-Mateos, Carlos; Terrón, Fernando; Herling, Marco

doi:10.3389/fonc.2021.736758

Cited by 12 publications

(4 citation statements)

References 281 publications

(603 reference statements)

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“…However, Wozniak et al did not detect CCR7 suppression by the medication. CCR7 is another homing chemokine receptor expressed by dendritic cells and T-cells that induces migration and invasion of malignant cells into lymph nodes through its ligand, CCL21, which is present on lymphatic vessels [32]. The expression of CCR7 has been shown to be a marker of advanced MF and has been correlated with subcutaneous involvement [33].…”

Section: Discussionmentioning

confidence: 99%

Differential Response of Mycosis Fungoides Cells to Vorinostat

Bordeaux

Reddy

Lee

et al. 2023

IJMS

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Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma (CTCL) and is characterized by epidermotrophism of malignant CD4+ T-lymphocytes. When MF advances to a recurrent stage, patients require treatment with systemic therapies such as vorinostat, a histone deacetylase inhibitor. While vorinostat has been shown to exhibit anti-tumor activity in MF, its exact molecular mechanism has yet to be fully discerned. In the present study, we examined the transcriptomic and proteomic profiles of vorinostat treatment in two MF cell lines, Myla 2059 and HH. We find that vorinostat downregulates CTLA-4, CXCR4, and CCR7 in both cell lines, but its effect on several key pathways differs between the two MF cell lines. For example, vorinostat upregulates CCL5, CCR5, and CXCL10 expression in Myla cells but downregulates CCL5 and CXCL10 expression in HH cells. Furthermore, vorinostat upregulates IFN-γ and IL-23 signaling and downregulates IL-6, IL-7, and IL-15 signaling in Myla cells but does not affect these pathways in HH cells. Although Myla and HH represent established MF cell lines, their distinct tumor origin from separate patients demonstrates that inherent phenotypic variations within the disease persist, underscoring the importance of using a variety of MF cells in the preclinical development of MF therapeutics.

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Section: Discussionmentioning

confidence: 99%

Differential Response of Mycosis Fungoides Cells to Vorinostat

Bordeaux

Reddy

Lee

et al. 2023

IJMS

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“…It is worth noting, that following lentiviral transduction and expansion protocols used in creation of the cell product, CCR7 + CD45RA + CAR T-cells likely do not have the same functional capacity as compared to non-genetically modified naïve T-cells ( 30 ). In our cohort, the great majority of both CD4 + and CD8 + CAR T-cells expressed CCR7, thus likely retaining their ability to enter lymph nodes which represents an important aspect of their potency to clear lymphatic tumors ( 31 , 32 ).…”

Section: Discussionmentioning

confidence: 85%

Brief research report: in-depth immunophenotyping reveals stability of CD19 CAR T-cells over time

Odak,

Bayir,

Riemann

et al. 2024

Front. Immunol.

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Variability or stability might have an impact on treatment success and toxicity of CD19 CAR T-cells. We conducted a prospective observational study of 12 patients treated with Tisagenlecleucel for CD19+ B-cell malignancies. Using a 31-color spectral flow cytometry panel, we analyzed differentiation stages and exhaustion markers of CAR T-cell subsets prior to CAR T-cell infusion and longitudinally during 6 months of follow-up. The majority of activation markers on CAR T-cells showed stable expression patterns over time and were not associated with response to therapy or toxicity. Unsupervised cluster analysis revealed an immune signature of CAR T-cell products associated with the development of immune cell-associated neurotoxicity syndrome. Warranting validation in an independent patient cohort, in-depth phenotyping of CAR T-cell products as well as longitudinal monitoring post cell transfer might become a valuable tool to increase efficacy and safety of CAR T-cell therapy.

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“…CCR7 has been strongly implicated in LN homing 17 and we next assessed whether higher levels of CCR7 on CXCR4 hi CD5 hi cells confer a greater propensity to migrate towards CCL21. When examining the bulk population, U-CLL cells migrated more efficiently in transwell assays than M-CLL cells at higher concentrations of CCL21, whilst no differences were detected at lower CCL21 concentrations (Supp Fig.5c).…”

Section: Resultsmentioning

confidence: 99%

Proliferating CLL cells express high levels of CXCR4 and CD5

Friedman,

Mehtani,

Vidler

et al. 2023

Preprint

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Chronic Lymphocytic Leukaemia (CLL) is an incurable progressive malignancy of CD5+ B cells with a birth rate between 0.1-1% of the entire clone per day. However, the phenotype and functional characteristics of proliferating CLL cells remain incompletely understood. Here, we stained peripheral blood CLL cells for ki67 and DNA content and found that CLL cells in G1-phase have a CXCR4loCD5hiphenotype, whilst CLL cells in S/G2/M-phase express high levels of both CXCR4 and CD5. Induction of proliferationin vitrousing CD40L stimulation results in high ki67 levels in CXCR4loCD5hicells with CXCR4 expression increasing as CLL cells progress through S and G2/M-phases, whilst CXCR4hiCD5loCLL cells remained quiescent. Dye dilution experiments revealed an accumulation of Ki67hidivided cells in the CXCR4hiCD5hifraction. In Eμ-TCL1 transgenic mice, the CXCR4hiCD5hifraction expressed high levels of ki67 and was expanded in enlarged spleens of diseased animals. Human peripheral blood CXCR4hiCD5hiCLL cells express high levels of IgM and the chemokine receptors CCR7 and CXCR5 and migrated most efficiently towards CCL21. We found higher levels of CXCR4 in patients with progressive disease and the CXCR4hiCD5hifraction was expanded upon clinical relapse. Thus, this study defines the phenotype and functional characteristics of proliferating CLL cells identifying a novel subclonal population that underlies CLL pathogenesis and may drive clinical outcome.

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CCR7 in Blood Cancers – Review of Its Pathophysiological Roles and the Potential as a Therapeutic Target

Cited by 12 publications

References 281 publications

Differential Response of Mycosis Fungoides Cells to Vorinostat

Differential Response of Mycosis Fungoides Cells to Vorinostat

Brief research report: in-depth immunophenotyping reveals stability of CD19 CAR T-cells over time

Proliferating CLL cells express high levels of CXCR4 and CD5

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