Abstract
Immunotherapy harnessing the host immune system for tumor destruction revolutionized oncology research and advanced treatment strategies for lymphoma patients. Lymphoma is a heterogeneous group of cancer, where the central roles in pathogenesis play immune evasion and dysregulation of multiple signaling pathways. Immunotherapy-based approaches such as engineered T cells (CAR T), immune checkpoint modulators and NK cell-based therapies are now in the frontline of lymphoma research. Even though emerging immunotherapies showed promising results in treating lymphoma patients, low efficacy and on-target/off-tumor toxicity are of a major concern. To address that issue it is suggested to look into the emerging role of heat shock proteins. Heat shock proteins (HSPs) showed to be highly expressed in lymphoma cells. HSPs are known for their abilities to modulate immune responses and inhibit apoptosis, which made their successful entry into cancer clinical trials. Here, we explore the role of HSPs in Hodgkin and Non-Hodgkin lymphoma and their involvement in CAR T therapy, checkpoint blockade and NK cell- based therapies. Understanding the role of HSPs in lymphoma pathogenesis and the ways how HSPs may enhance anti-tumor responses, may help in the development of more effective, specific and safe immunotherapy.
Highlights
Lymphoma is a heterogeneous cancer divided into two major types such as Hodgkin lymphoma (HL) and Non-Hodgkin lymphoma (NHL) [1, 2]
We focus on the role of Heat shock proteins (HSPs) family in Hodgkin and Non-Hodgkin lymphoma
Jacobson and colleagues reported that HSP90 inhibition led to the complete loss of Bruton tyrosine kinase (BTK) and IKKa and downstream loss of phosphorylated ERK1/2 in mantle cell lymphoma cell lines [106].HSP90 inhibitor showed to downregulate BTK in cells expressing BTK C481S mutation, which was found to be associated with resistance to BTK inhibitor ibrutinib in MCL and chronic lymphocytic leukemia (CLL) patients [106,107,108]
Summary
Lymphoma is a heterogeneous cancer divided into two major types such as Hodgkin lymphoma (HL) and Non-Hodgkin lymphoma (NHL) [1, 2]. Aberrant expression of mitogen-activated protein kinase (MAPK)/ERK has been reported in HL [88].In light of the reported, HSP90 inhibitor 17-AAG showed to deplete AKT and inhibit extracellular signal-regulated kinase (ERK) phosphorylation, leading to growth arrest and apoptosis in HL cell lines [89] [88].
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