Checkpoint inhibitors in hematological malignancies

• Published in: Journal of hematology and oncology Vol. 10; no. 1; p. 103
• Main Authors: Ok, Chi Young, Young, Ken H
• Format: Journal Article
• Language: English
• Published: England BioMed Central 08.05.2017; BMC
• Subjects: Acute myeloid leukemia; Antigen-Presenting Cells - immunology; Antigens; Antigens, CD - drug effects; Antigens, CD - physiology; Antineoplastic Agents, Immunological - adverse effects; Antineoplastic Agents, Immunological - therapeutic use; Apoptosis; B7-H1 Antigen - antagonists & inhibitors; B7-H1 Antigen - physiology; Binding sites; Biology; Biomarkers; Biomarkers, Tumor; Blood cancer; CD223 antigen; Clinical trials; Clinical Trials as Topic; CTLA-4; CTLA-4 Antigen - antagonists & inhibitors; CTLA-4 Antigen - physiology; CTLA-4 protein; Cytotoxicity; Epstein-Barr virus; Hematologic malignancies; Hematologic Neoplasms - drug therapy; Hematology; Hepatitis A Virus Cellular Receptor 2 - antagonists & inhibitors; Hepatitis A Virus Cellular Receptor 2 - physiology; Hodgkin's lymphoma; Humans; Immune checkpoint; Immune checkpoint inhibitors; Immune response; Immunoglobulins; Immunology; Immunosurveillance; Immunotherapy; Janus kinase 2; Ligands; Lung cancer; Lymphocyte Activation - drug effects; Lymphocyte Activation Gene 3 Protein; Lymphocytes; Lymphoma; Melanoma; Molecular Targeted Therapy; Multicenter Studies as Topic; Myelodysplastic syndrome; Myeloid leukemia; Myeloma; Neoplasm Proteins - antagonists & inhibitors; Oncology; Patient Selection; PD-1; PD-1 protein; PD-L1; PD-L1 protein; PD-L2; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Programmed Cell Death 1 Receptor - physiology; Proteins; Recovery of function; Review; T cell receptors; Tumor Escape - drug effects; PD-L1; PD-L2; Hematologic malignancies; CTLA-4; Immune checkpoint; PD-1
• ISSN: 1756-8722; 1756-8722
• DOI: 10.1186/s13045-017-0474-3

Inhibitory molecules such as PD-1, CTLA-4, LAG-3, or TIM-3 play a role to keep a balance in immune function. However, many cancers exploit such molecules to escape immune surveillance. Accumulating data support that their functions are dysregulated in lymphoid neoplasms, including plasma cell myeloma, myelodysplastic syndrome, and acute myeloid leukemia. In lymphoid neoplasms, aberrations in 9p24.1 (PD-L1, PD-L2, and JAK2 locus), latent Epstein-Barr virus infection, PD-L1 3'-untranslated region disruption, and constitutive JAK-STAT pathway are known mechanisms to induce PD-L1 expression in lymphoma cells. Clinical trials demonstrated that PD-1 blockade is an attractive way to restore host's immune function in hematological malignancies, particularly classical Hodgkin lymphoma. Numerous clinical trials exploring PD-1 blockade as a single therapy or in combination with other immune checkpoint inhibitors in patients with hematologic cancers are under way. Although impressive clinical response is observed with immune checkpoint inhibitors in patients with certain cancers, not all patients respond to immune checkpoint inhibitors. Therefore, to identify best candidates who would have excellent response to checkpoint inhibitors is of utmost importance. Several possible biomarkers are available, but consensus has not been made and pursuit to discover the best biomarker is ongoing.