title: Immune checkpoint blockade: Releasing the brake towards hematological malignancies.
abstract: Tumor cells utilize co-inhibitory molecules to avoid host immune destruction. Checkpoint blockade has emerged as a promising approach to treat cancer by restoring T cell effector function and breaking a tumor permissive microenvironment. Patients with hematological malignancies often have immune dysregulation, thus the role of checkpoint blockade in treatment of these neoplasms is particularly intriguing. In early trials, antibodies targeting cytotoxic T lymphocyte antigen 4 (CTLA-4) or the programmed death 1 (PD-1) signaling pathway have displayed significant efficacy with minimal toxicity in patients with relapsed and refractory hematological neoplasms. In this review, we provide evidence of dysregulation of CTLA-4 and PD-1/PD-Ls in the context of several major types of hematological neoplasms and summarize relevant clinical practice points for checkpoint blockade. The preclinical rationale and preliminary clinical data of potential combination approaches designed to optimize checkpoint antagonists are well presented.
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; The University of Texas Graduate School of Biomedical Science, Houston, TX, USA. Electronic address: khyoung@mdanderson.org.
authors.forename: Ken H
authors.initials: KH
authors.lastname: Young
mesh_terms: D000818:Animals; D000074322:Antineoplastic Agents, Immunological / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors*; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects*; D058990:Molecular Targeted Therapy; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000037:antagonists & inhibitors; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000074322:Antineoplastic Agents, Immunological; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; D060908:CTLA-4 Antigen; C556977:PDCD1LG2 protein, human; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor
keywords: Lymphoid malignancies; Nivolumab; PD-1; PD-L1; PD-L2; Pembrolizumab; Pidilizumab