Checkpoint blockade in solid tumors and B-cell malignancies, with special consideration of the role of CD200

Abstract

In the ontogeny of a normal immune response, a series of checkpoints must be overcome to ensure that unwanted and/or harmful self-directed activation responses are avoided. Many of the molecules now known to be active in this overseeing of the evolving immune activation cascade, contributing inhibitory signals to dampen an overexuberant response, belong to the immunoglobulin supergene family. These include members of the CD28/CTLA-4:B7.1/B7.2 receptor/ligand family, PD-1 and PDL-1, CD200 and CD200R, and the more recently described V-domain immunoglobulin suppressor of T-cell activation and its ligand (VSIG-3/IGSF11). Unfortunately, from the point of view of improving immunotargeting of cancer cells, triggering these checkpoint inhibitory signaling pathways, so necessary to maintain self-tolerance, simultaneously acts to prevent effective tumor immunity. The recent development of reagents, predominantly antibodies, to act as checkpoint blockade agents, has had a dramatic effect on human cancer treatment, with a marked reported success for anti-CTLA-4 and PD-1 in particular in clinical trials. This review provides a general overview of the data now available showing the promise of such treatments to our cancer armamentarium and elaborates in depth on the potential promise of what can be regarded as an underappreciated target molecule for checkpoint blockade in chronic lymphocytic leukemia and solid tumors, CD200.

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

“…Moreover, the findings in the current study demonstrated that CD200 positive expression was an independent predictor of MDS transformation to acute myeloid leukemia. These findings were in parallel with that reported in the previous studies which confirmed the prognostic relevance of high CD200 expression in MDS patients (Tiribelli et al, 2017;Gorczynski et al .,2017;Coles et al ., 2012).…”

Inflammation and transcriptional responses of peripheral blood mononuclear cells in classic ataxia telangiectasia

“…These genes include the immune and tumor suppressor genes, ADAM23 [27] and BACH2 [28] and CD200, a molecule that helps to regulate immune activation. [29] All three of these genes were downregulated in the A-T subjects.…”

Transcriptome analysis of desmoplastic small round cell tumors identifies actionable therapeutic targets: a report from the Children’s Oncology Group

“…The expression of CD200R is restricted predominantly to cells of macrophage and myeloid lineage. CD200-CD200R pathway in the context of tumors has been most extensively studied in hematologic malignancies such as mature B-cell neoplasms, CLL and AML 33 . In solid tumors, CD200 expression has been demonstrated on ovarian cancer, melanoma, neuroblastoma and renal cancer cell lines 34 .…”