Impaired Heat Shock Protein Expression in Activated T Cells in B-Cell Lymphoma
Albakova Z. Mangasarova Y. Sapozhnikov A.
November 2022MDPI
Biomedicines
2022#10Issue 11
Heat shock proteins (HSPs) are molecular chaperones that act in a variety of cellular processes, ensuring protein homeostasis and integrity. HSPs play critical roles in the modulation of various immune cells. However, the role of HSPs in T cell activation is largely unknown. We show that HSPs are upregulated following CD3/CD28 stimulation, suggesting that HSP expression might be regulated via TCR. We found that B-cell lymphoma (BCL) patients have dysregulated expression of intracellular and extracellular HSPs, immune checkpoints PD-1, CTLA-4, and STAT3 in CD3/CD28-activated T cells. Consistent with previous findings, we show that HSP90 inhibition downregulated CD4 and CD8 surface markers in healthy controls and BCL patients. HSP90 inhibition alone or in combination with PD-1 or CTLA-4 inhibitors differentially affected CD4+ and CD8+ T cell degranulation responses when stimulated with allogeneic DCs or CD3/CD28 in BCL patients. Additionally, we showed that HSP90 inhibition does not significantly affect intracellular PD-1 and CTLA-4 expression in CD3/CD28-activated T cells. These findings may provide the basis for the discovery of novel immunological targets for the treatment of cancer patients and improve our understanding of HSP functions in immune cells.
extracellular HSPs , heat shock proteins , HSP60 , HSP70 , HSP90 , lymphoma , T cells
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Department of Biology, Lomonosov Moscow State University, Moscow, 119192, Russian Federation
Chokan Limited Liability Partnership (LLP), Almaty, 050039, Kazakhstan
National Medical Research Center for Hematology, Moscow, 125167, Russian Federation
Department of Immunology, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, 117997, Russian Federation
Department of Biology
Chokan Limited Liability Partnership (LLP)
National Medical Research Center for Hematology
Department of Immunology
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