γδ T cell-mediated cytotoxicity against patient-derived healthy and cancer cervical organoids
Frontiers in Immunology, ISSN: 1664-3224, Vol: 14, Page: 1281646
2023
- 3Citations
- 19Captures
- 1Mentions
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- Citations3
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- Captures19
- Readers19
- 19
- Mentions1
- News Mentions1
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Most Recent News
Recent Studies from Christian-Albrechts-Universitat zu Kiel Add New Data to Cervical Cancer (gd T cell-mediated cytotoxicity against patient-derived healthy and cancer cervical organoids)
2023 DEC 07 (NewsRx) -- By a News Reporter-Staff News Editor at NewsRx Women's Health Daily -- Data detailed on cervical cancer have been presented.
Article Description
Cervical cancer is a leading cause of death among women globally, primarily driven by high-risk papillomaviruses. However, the effectiveness of chemotherapy is limited, underscoring the potential of personalized immunotherapies. Patient-derived organoids, which possess cellular heterogeneity, proper epithelial architecture and functionality, and long-term propagation capabilities offer a promising platform for developing viable strategies. In addition to αβ T cells and natural killer (NK) cells, γδ T cells represent an immune cell population with significant therapeutic potential against both hematologic and solid tumours. To evaluate the efficacy of γδ T cells in cervical cancer treatment, we generated patient-derived healthy and cancer ectocervical organoids. Furthermore, we examined transformed healthy organoids, expressing HPV16 oncogenes E6 and E7. We analysed the effector function of in vitro expanded γδ T cells upon co-culture with organoids. Our findings demonstrated that healthy cervical organoids were less susceptible to γδ T cell-mediated cytotoxicity compared to HPV-transformed organoids and cancerous organoids. To identify the underlying pathways involved in this observed cytotoxicity, we performed bulk-RNA sequencing on the organoid lines, revealing differences in DNA-damage and cell cycle checkpoint pathways, as well as transcription of potential γδ T cell ligands. We validated these results using immunoblotting and flow cytometry. We also demonstrated the involvement of BTN3A1 and BTN2A1, crucial molecules for γδ T cell activation, as well as differential expression of PDL1/CD274 in cancer, E6/E7+ and healthy organoids. Interestingly, we observed a significant reduction in cytotoxicity upon blocking MSH2, a protein involved in DNA mismatch-repair. In summary, we established a co-culture system of γδ T cells with cervical cancer organoids, providing a novel in vitro model to optimize innovative patient-specific immunotherapies for cervical cancer.
Bibliographic Details
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85179345032&origin=inward; http://dx.doi.org/10.3389/fimmu.2023.1281646; http://www.ncbi.nlm.nih.gov/pubmed/38090581; https://www.frontiersin.org/articles/10.3389/fimmu.2023.1281646/full; https://dx.doi.org/10.3389/fimmu.2023.1281646; https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1281646/full
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