Impaired Heat Shock Protein Expression in Activated T Cells in B-Cell Lymphoma.
| Autor: | Albakova Z; Department of Biology, Lomonosov Moscow State University, Moscow 119192, Russia.; Chokan Limited Liability Partnership (LLP), Almaty 050039, Kazakhstan., Mangasarova Y; National Medical Research Center for Hematology, Moscow 125167, Russia., Sapozhnikov A; Department of Biology, Lomonosov Moscow State University, Moscow 119192, Russia.; Department of Immunology, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow 117997, Russia. |
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| Jazyk: | angličtina |
| Zdroj: | Biomedicines [Biomedicines] 2022 Oct 28; Vol. 10 (11). Date of Electronic Publication: 2022 Oct 28. |
| DOI: | 10.3390/biomedicines10112747 |
| Abstrakt: | 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. Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. |
| Databáze: | MEDLINE |
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