Prognostic and Predictive Values of CD155 in Patients With Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy. It is the most common form of acute leukemia among adults. In the United States, an estimated 19,940 people will be diagnosed with AML in 2020.

T-cell exhaustion is a state of decline in T-cell proliferation and function (secretion of cytokines and cytotoxicity). It is defined by the expression of immune checkpoints including programmed cell death protein-1 (PD1), cytotoxic T-lymphocyte-associated protein-4 (CTLA4), T-cell immunoglobulin and mucin-domain containing-3 (TIM3), lymphocyte-activation gene-3 (LAG3), T-cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT), and CD160. This phenomenon was observed in many cancer cells to escape from antitumor immune responses.

The poliovirus receptor (PVR), also known as CD155, is an immunoglobulin -like adhesion molecule, with an important regulatory role in T-cell and natural killer (NK) cell functions, cell migration and proliferation. It is a major ligand that is expressed on epithelial and myeloid cells of the tumor. PVR is able to bind CD226, DNAX accessory molecule-1 (DNAM-1), T-cell-Activated Increased Late Expression Protein (TACTILE), and TIGIT. Binding to DNAM-1 induces the release of pro-inflammatory cytokines and cytotoxicity of T-cells and NK cells (T-cell activation), while binding to TIGIT induces a rather anti-inflammatory, non-proliferative, and noncytotoxic profile (T-cell exhaustion).

CD155 expression was associated with an unfavorable prognosis in solid tumors such as colon cancer, breast cancer, lung adenocarcinoma, pancreatic cancer, melanoma, and glioblastoma, as it correlated with tumor migration, development of metastases, tissue and lymph node invasion, relapse, and poorer survival.

Stamm et al., demonstrated that high CD155 (PVR) expression correlated with poor outcome in AML. Stamm et al., also showed that antibody blockade of PVR on AML cell lines or primary AML cells or TIGIT blockade on immune cells increased the anti-leukemic effects mediated by purified CD3+ cells in vitro. Zhang et al., assessed the prognostic significance and immune-associated mechanism of CD155 and identified that CD155 was commonly upregulated in most human cancers including AML, and high expression of CD155 was closely correlated with unfavorable clinical outcomes.