Impacts of combining anti-PD-L1 immunotherapy and radiotherapy on the tumour immune microenvironment in a murine prostate cancer model
<p><strong>Background</strong></p> <p>Radiotherapy enhances innate and adaptive anti-tumour immunity. It is unclear whether this effect may be harnessed by combining immunotherapy with radiotherapy fractions used to treat prostate cancer. We investigated tumour immune m...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Springer Nature
2020
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| _version_ | 1797066052803231744 |
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| author | Philippou, Y Sjoberg, HT Murphy, E Alyacoubi, S Jones, KI Gordon-Weeks, AN Phyu, S Parkes, EE McKenna, WG Lamb, AD Gileadi, U Cerundolo, V Scheiblin, DA Lockett, SL Wink, DA Mills, IG Hamdy, FC Muschel, RJ Bryant, RJ |
| author_facet | Philippou, Y Sjoberg, HT Murphy, E Alyacoubi, S Jones, KI Gordon-Weeks, AN Phyu, S Parkes, EE McKenna, WG Lamb, AD Gileadi, U Cerundolo, V Scheiblin, DA Lockett, SL Wink, DA Mills, IG Hamdy, FC Muschel, RJ Bryant, RJ |
| author_sort | Philippou, Y |
| collection | OXFORD |
| description | <p><strong>Background</strong></p>
<p>Radiotherapy enhances innate and adaptive anti-tumour immunity. It is unclear whether this effect may be harnessed by combining immunotherapy with radiotherapy fractions used to treat prostate cancer. We investigated tumour immune microenvironment responses of pre-clinical prostate cancer models to radiotherapy. Having defined this landscape, we tested whether radiotherapy-induced tumour growth delay could be enhanced with anti-PD-L1.</p>
<p><strong>Methods</strong></p>
<p>Hypofractionated radiotherapy was delivered to TRAMP-C1 and MyC-CaP flank allografts. Tumour growth delay, tumour immune microenvironment flow-cytometry, and immune gene expression were analysed. TRAMP-C1 allografts were then treated with 3 × 5 Gy ± anti-PD-L1.</p>
<p><strong>Results</strong></p>
<p>3 × 5 Gy caused tumour growth delay in TRAMP-C1 and MyC-CaP. Tumour immune microenvironment changes in TRAMP-C1 at 7 days post-radiotherapy included increased tumour-associated macrophages and dendritic cells and upregulation of PD-1/PD-L1, CD8+ T-cell, dendritic cell, and regulatory T-cell genes. At tumour regrowth post-3 × 5 Gy the tumour immune microenvironment flow-cytometry was similar to control tumours, however CD8+, natural killer and dendritic cell gene transcripts were reduced. PD-L1 inhibition plus 3 × 5 Gy in TRAMP-C1 did not enhance tumour growth delay versus monotherapy.</p>
<p><strong>Conclusion</strong></p>
<p>3 × 5 Gy hypofractionated radiotherapy can result in tumour growth delay and immune cell changes in allograft prostate cancer models. Adjuncts beyond immunomodulation may be necessary to improve the radiotherapy-induced anti-tumour response.</p> |
| first_indexed | 2024-03-06T21:36:51Z |
| format | Journal article |
| id | oxford-uuid:468e4541-4849-4fbe-97c3-258c560e35aa |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:36:51Z |
| publishDate | 2020 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:468e4541-4849-4fbe-97c3-258c560e35aa2022-03-26T15:14:27ZImpacts of combining anti-PD-L1 immunotherapy and radiotherapy on the tumour immune microenvironment in a murine prostate cancer modelJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:468e4541-4849-4fbe-97c3-258c560e35aaEnglishSymplectic ElementsSpringer Nature2020Philippou, YSjoberg, HTMurphy, EAlyacoubi, SJones, KIGordon-Weeks, ANPhyu, SParkes, EEMcKenna, WGLamb, ADGileadi, UCerundolo, VScheiblin, DALockett, SLWink, DAMills, IGHamdy, FCMuschel, RJBryant, RJ<p><strong>Background</strong></p> <p>Radiotherapy enhances innate and adaptive anti-tumour immunity. It is unclear whether this effect may be harnessed by combining immunotherapy with radiotherapy fractions used to treat prostate cancer. We investigated tumour immune microenvironment responses of pre-clinical prostate cancer models to radiotherapy. Having defined this landscape, we tested whether radiotherapy-induced tumour growth delay could be enhanced with anti-PD-L1.</p> <p><strong>Methods</strong></p> <p>Hypofractionated radiotherapy was delivered to TRAMP-C1 and MyC-CaP flank allografts. Tumour growth delay, tumour immune microenvironment flow-cytometry, and immune gene expression were analysed. TRAMP-C1 allografts were then treated with 3 × 5 Gy ± anti-PD-L1.</p> <p><strong>Results</strong></p> <p>3 × 5 Gy caused tumour growth delay in TRAMP-C1 and MyC-CaP. Tumour immune microenvironment changes in TRAMP-C1 at 7 days post-radiotherapy included increased tumour-associated macrophages and dendritic cells and upregulation of PD-1/PD-L1, CD8+ T-cell, dendritic cell, and regulatory T-cell genes. At tumour regrowth post-3 × 5 Gy the tumour immune microenvironment flow-cytometry was similar to control tumours, however CD8+, natural killer and dendritic cell gene transcripts were reduced. PD-L1 inhibition plus 3 × 5 Gy in TRAMP-C1 did not enhance tumour growth delay versus monotherapy.</p> <p><strong>Conclusion</strong></p> <p>3 × 5 Gy hypofractionated radiotherapy can result in tumour growth delay and immune cell changes in allograft prostate cancer models. Adjuncts beyond immunomodulation may be necessary to improve the radiotherapy-induced anti-tumour response.</p> |
| spellingShingle | Philippou, Y Sjoberg, HT Murphy, E Alyacoubi, S Jones, KI Gordon-Weeks, AN Phyu, S Parkes, EE McKenna, WG Lamb, AD Gileadi, U Cerundolo, V Scheiblin, DA Lockett, SL Wink, DA Mills, IG Hamdy, FC Muschel, RJ Bryant, RJ Impacts of combining anti-PD-L1 immunotherapy and radiotherapy on the tumour immune microenvironment in a murine prostate cancer model |
| title | Impacts of combining anti-PD-L1 immunotherapy and radiotherapy on the tumour immune microenvironment in a murine prostate cancer model |
| title_full | Impacts of combining anti-PD-L1 immunotherapy and radiotherapy on the tumour immune microenvironment in a murine prostate cancer model |
| title_fullStr | Impacts of combining anti-PD-L1 immunotherapy and radiotherapy on the tumour immune microenvironment in a murine prostate cancer model |
| title_full_unstemmed | Impacts of combining anti-PD-L1 immunotherapy and radiotherapy on the tumour immune microenvironment in a murine prostate cancer model |
| title_short | Impacts of combining anti-PD-L1 immunotherapy and radiotherapy on the tumour immune microenvironment in a murine prostate cancer model |
| title_sort | impacts of combining anti pd l1 immunotherapy and radiotherapy on the tumour immune microenvironment in a murine prostate cancer model |
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