Harnessing tumor immunity with cytotoxics : T cells monitoring in mice bearing lung tumors treated with anti-VEGF and pemetrexed-cisplatin doublet
© 2023. The Author(s), under exclusive licence to Springer Nature Limited..
BACKGROUND: Successful immunotherapy is restricted to some cancers only, and combinatorial strategies with other drugs could help to improve their efficacy. Here, we monitor T cells in NSCLC model after treatment with cytotoxics (CT) and anti-VEGF drugs, to understand when immune checkpoint inhibitors should be best associated next.
METHODS: In vivo study was performed on BALB/c mice grafted with KLN205 cells. Eight treatments were tested including control, cisplatin and pemetrexed as low (LD CT) and full (MTD CT) dose as single agents, flat dose anti-VEGF and the association anti-VEGF + CT. Full immunomonitoring was performed by flow cytometry on tumor, spleen and blood over 3 weeks.
RESULTS: Immunomodulatory effect was dependent upon both treatments and time. In tumors, combination groups shown numerical lower Treg cells on Day 21. In spleen, anti-VEGF and LD CT group shown higher CD8/Treg ratio on Day 7; on Day 14, higher T CD4 were observed in both combination groups. Finally, in blood, Tregs were lower and CD8/Treg ratio higher, on Day 14 in both combination groups. On Day 21, CD4 and CD8 T cells were higher in the anti-VEGF + MTD CT group.
CONCLUSIONS: Anti-VEGF associated to CT triggers notable increase in CD8/Tregs ratio. Regarding the scheduling, a two-week delay after using anti-VEGF and CT could be the best sequence to optimize antitumor efficacy.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:129 |
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| Enthalten in: |
British journal of cancer - 129(2023), 9 vom: 31. Okt., Seite 1373-1382 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sicard, G [VerfasserIn] |
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| Links: |
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| Themen: |
04Q9AIZ7NO |
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| Anmerkungen: |
Date Completed 08.11.2023 Date Revised 09.11.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41416-023-02350-7 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM360247830 |
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| 520 | |a © 2023. The Author(s), under exclusive licence to Springer Nature Limited. | ||
| 520 | |a BACKGROUND: Successful immunotherapy is restricted to some cancers only, and combinatorial strategies with other drugs could help to improve their efficacy. Here, we monitor T cells in NSCLC model after treatment with cytotoxics (CT) and anti-VEGF drugs, to understand when immune checkpoint inhibitors should be best associated next | ||
| 520 | |a METHODS: In vivo study was performed on BALB/c mice grafted with KLN205 cells. Eight treatments were tested including control, cisplatin and pemetrexed as low (LD CT) and full (MTD CT) dose as single agents, flat dose anti-VEGF and the association anti-VEGF + CT. Full immunomonitoring was performed by flow cytometry on tumor, spleen and blood over 3 weeks | ||
| 520 | |a RESULTS: Immunomodulatory effect was dependent upon both treatments and time. In tumors, combination groups shown numerical lower Treg cells on Day 21. In spleen, anti-VEGF and LD CT group shown higher CD8/Treg ratio on Day 7; on Day 14, higher T CD4 were observed in both combination groups. Finally, in blood, Tregs were lower and CD8/Treg ratio higher, on Day 14 in both combination groups. On Day 21, CD4 and CD8 T cells were higher in the anti-VEGF + MTD CT group | ||
| 520 | |a CONCLUSIONS: Anti-VEGF associated to CT triggers notable increase in CD8/Tregs ratio. Regarding the scheduling, a two-week delay after using anti-VEGF and CT could be the best sequence to optimize antitumor efficacy | ||
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| 700 | 1 | |a Ciccolini, J |e verfasserin |4 aut | |
| 700 | 1 | |a Fanciullino, R |e verfasserin |4 aut | |
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