Modulatory effects of bortezomib on host immune cell functions.
Bortezomib is an inhibitor of the ubiquitin-proteasome proteolytic pathway responsible for intracellular protein turnover. Cellular proteins controlled by this pathway represent a diverse group of potential therapeutic targets, particularly in cancer cells, which exploit this proteasomal pathway to promote their growth and diminish apoptosis. Along with inhibiting the proteasome and thus sensitizing tumor cells to apoptosis, bortezomib may also have multiple effects on the host immune responses. This review summarizes the effects that bortezomib may play on immune cell subsets in various disease states in modifying lymphocyte receptors, ligands, the expression of various cytokines and chemokines and their downstream signaling. We also propose steps that can be taken to refine combinatorial strategies that include bortezomib to improve current immunotherapeutic approaches.
Department of Biochemistry & Cancer Biology, School of Medicine, Meharry Medical College, Nashville, TN 37208, USA.|School of Graduate Studies & Research, Meharry Medical College, Nashville, TN 37208, USA.|Department of Microbiology & Immunology, School of Medicine, Meharry Medical College, Nashville, TN 37208, USA.
Samuel Troy
ST
Pellom
Department of Biochemistry & Cancer Biology, School of Medicine, Meharry Medical College, Nashville, TN 37208, USA.
Duafalia Fred
DF
Dudimah
Department of Biochemistry & Cancer Biology, School of Medicine, Meharry Medical College, Nashville, TN 37208, USA.
Menaka Chanu
MC
Thounaojam
Cancer & Inflammation Program, National Cancer Institute, Frederick, MD 21702, USA.|Basic Sciences Program, Leidos Biomedical Research, Inc., Frederick, MD 21702, USA.
Thomas Joseph
TJ
Sayers
Department of Biochemistry & Cancer Biology, School of Medicine, Meharry Medical College, Nashville, TN 37208, USA.|School of Graduate Studies & Research, Meharry Medical College, Nashville, TN 37208, USA.|Host-Tumor Interactions Research Program, Vanderbilt-Ingram Comprehensive Cancer Center, Vanderbilt University, Nashville, TN 37232, USA.
Anil
A
Shanker
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069286:Bortezomib / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007167:Immunotherapy; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D025801:Ubiquitin / Q000378:metabolism
D016207:Cytokines; D025801:Ubiquitin; D000069286:Bortezomib; D046988:Proteasome Endopeptidase Complex
B cells; NK cells; T cells; bortezomib; chemokine; cytokine; dendritic cells; immunity; inflammation; ligands; lymphocyte receptors