Novel target and treatment agents for natural killer/T-cell lymphoma

Abstract

The rapidly increasing use of high-throughput screening had produced a plethora of expanding knowledge on the molecular basis of natural killer/T-cell lymphoma (NKTCL), which in turn has revolutionized the treatment. Specifically, the use of asparaginase-containing regimens has led to substantial improvement in survival outcomes in NKTCL patients. Novel treatment strategies that are currently under development include cell-surface-targeted antibodies, immune checkpoint inhibitors, Epstein-Barr virus targeted cytotoxic T lymphocyte, immunomodulatory agents, chimeric antigen receptor T cells, signaling pathway inhibitors and epigenetic targeted agents. In almost all cases, initial clinical studies of newly developed treatment are conducted in patients relapsed, and refractory NKTCL due to very limited treatment options. This review summarizes the results of these novel treatments for NKTCL and discusses their potential for likely use in NKTCL in a wider setting in the future.

Anti-metabolic agent pegaspargase plus PD-1 antibody sintilimab for first-line treatment in advanced natural killer T cell lymphoma

“…Metabolic reprogramming, immune suppression, epigenetic dysregulation, cell-cycle progression, cell death resistance and sustaining proliferation were hallmark characteristics during the pathogenesis of NKTCL. 47 Pegasparagase-containing chemotherapies, dual targeting metabolic reprogramming and cell-cycle progression, showed efficacy in treating patients relapsed from or refractory to chemo-free pegarspargase and sintilimab regimen. In addition to malignant transformation, epigenetic dysregulation contributed to exhausted T cell phenotype, 48 indicating therapeutic potential of checkpoint blockade in combination with epigenetic modifiers.…”

“…In addition to malignant transformation, epigenetic dysregulation contributed to exhausted T cell phenotype, 48 indicating therapeutic potential of checkpoint blockade in combination with epigenetic modifiers. With the expanding knowledge on the pathogenic mechanism of NKTCL, a plethora of novel treatment strategies, including cell-surface-targeted antibodies, chimeric antigen receptor T cells, EBV-specific T lymphocyte, signaling pathway inhibitors and epigenetic drugs, 47 are under development for future molecular signature-guided targeted therapies.…”

Extranodal lymphoma: pathogenesis, diagnosis and treatment

“…The JAK/STAT pathway mediates the transmission of signals from cytokines and growth factors. Dysregulation of this pathway has been observed in extranodal lymphomas, including mucosa-associated lymphoid tissue (MALT) lymphomas, natural killer/T-cell lymphoma (nasal type, NKTCL-NT) [ 13 , 19 ], primary central nervous system lymphoma (PCNSL) [ 20 ] and peripheral T cell lymphoma (PTCL) [ 21 , 22 ]. The JAK/STAT pathway is associated with immune homeostasis, inflammation, cell proliferation, apoptosis and differentiation in extranodal lymphoma [ 21 ].…”