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Lysates from the probiotic bacterium Streptococcus thermophilus enhances the survival of T cells and triggers programmed cell death in neuroblastoma cells

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Abstract

Neuroblastoma is the most common brain solid tumor in infancy. Despite the availability of numerous approaches like immunotherapy, surgery, chemotherapy, and radiotherapy, neuroblastoma frequently develops resistance and recurs. Immunotherapy is one of the most promising approaches and PD-L1 antibody blocking is the phenomena used to inhibit PD-1 receptors to increase and improve cytotoxic T cells toward cancer. Numerous studies underlined the critical role of probiotics on immune system development and modulation in addition to possible role in inducing apoptosis in cancer cells. In this study, a Streptococcus thermophilus strain, isolated from a local yogurt, was used as it is considered a potential probiotic due to its tolerance lower pH, bile acid, antibiotic suitability, and blood hemolysis. Our results showed that S. thermophilus lysates played as an immune checkpoint modulator at 25 µg/ml dose boosting PD-L1 transcripts and protein levels in SH-SY5Y neuroblastoma cell line. Interestingly, co-culture between SH-SY5Y and Jurkat T cells in the presence of blocking PD-L1 antibodies increased Jurkat T-cell viability compering to control without lysate. On the other hand, annexin-V/7-AAD, qPCR and western blot results showed that S. thermophilus lysates at 200 and 400 µg/ml decreased SH-SY5Y cell viability and increased apoptotic marker genes transcription and caspase-3 and caspase-9 protein expression.

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Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Medical Biology, Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey

    Safaa Altves, Ilknur Cinar Ayan & Hasibe Vural

  2. Department of Basic Science and Health, Hemp Research Institute, Yozgat Bozok University, Yozgat, Turkey

    Ebru Guclu

  3. Department of Molecular Biology and Genetics, Faculty of Agriculture and Natural Sciences, Konya Food and Agriculture University, Konya, Turkey

    Kivanc Bilecen

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  1. Safaa Altves
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Contributions

SA, EG, ICA, KB, and HV conceived and designed the research. SA and KB performed bacterial isolation, identification as well as microbiological analysis. Molecular and anticancer activity analyses have been performed by EG, ICA, SA and HV. All authors analyzed data, read and approved the manuscript.

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Correspondence to Safaa Altves.

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Altves, S., Guclu, E., Cinar Ayan, I. et al. Lysates from the probiotic bacterium Streptococcus thermophilus enhances the survival of T cells and triggers programmed cell death in neuroblastoma cells. Med Oncol 40, 315 (2023). https://doi.org/10.1007/s12032-023-02186-4

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