Prognostic Value of CD200 Expression and Soluble CTLA-4 Concentrations in Intermediate and High-Risk Myelodysplastic Syndrome Patients

Abstract

The clinical course of Myelodysplastic Syndromes (MDS) are very heterogeneous, with a wide diversity in patient's outcome. Whilst near one third of MDS progress to AML; the other two thirds transformed from low risk into high risk MDS (Garcia-Manero 2015

Differential regulation of CTLA4 expression through BTK-dependent and independent mechanisms in CLL

“…41,42 Although this form of CTLA4 is less understood than membrane-bound CTLA4, it is elevated in various inflammatory conditions and malignancies, such as acute lymphoblastic leukemia, myelodysplastic syndrome, and AML, and has been implicated to be immunosuppressive. [43][44][45][46][47] We decided to test if this alternative isoform is expressed by CLL cells in addition to the full-length version of CTLA4. Interestingly, the alternatively spliced soluble CTLA4 transcript is detectable in CLL cells at similar threshold cycle to the full-length transcript, indicating that this transcript is also expressed in CLL cells (Figure 3A).…”

Updates on the Importance of CD200:CD200R Checkpoint Blockade in Solid Tumors and B cell Malignancies

“…There can be little doubt that immune checkpoint blockade has transformed cancer immunotherapy producing some quite remarkable and long-lasting effects, particularly in melanoma and some hematopoietic tumors and now expanding to multiple solid tumor studies. As has been highlighted, the use of genomic expression analysis has both guided characterization of the molecules involved, and helped gain insight into their mechanism(s) of action [65,68,73,74,79,87,92,[101][102][103]. As but one further example, analysis of sorted CD4 + CD26and CD4 + CD26 + T cells from classical Hodgkins Lymphoma lymph node cell suspensions (HLN) by RNA sequencing and T cell receptor variable gene segment usage analysis showed that while CD4 + CD26 -T cells were antigen experienced, they were not clonally expanded [113].…”

“…Before concluding this section on discussion of the importance of CD200:CD200R in control of myeloid tumors, it is worthy of note that even in studies where there was little direct evidence for a role of attenuating CD200 expression in tumor growth control, there has been reported value in monitoring expression in both the diagnosis of B cell malignancies [65,66], and in monitoring dynamic changes during the response to treatment [67]. This is the case also in high risk myelodysplastic patients [68]. A final comment, which will be elaborated on below in a discussion of the effect of CD200:CD200R interactions in solid tumors, concerns the potential importance of this dyad, beyond any direct effect on tumor cells themselves, in controlling tumor growth through regulation of the tumor microenvironment (TME) [69].…”

Immune checkpoints represent a promising breakthrough in targeted therapy and prognosis of myelodysplastic syndrome

“…Similar changing trend of CTLA-4+ cells could also be obtained in MDS patients. In a study involving 57 MDS patients, the serum level of CTLA-4 was increased and positively associated with the risk stratification in these patients [ 139 ].…”