Immunomodulatory response to neoadjuvant nivolumab in non-metastatic clear cell renal cell carcinoma
© 2024. The Author(s)..
Novel perioperative strategies are needed to reduce recurrence rates in patients undergoing nephrectomy for high-risk, non-metastatic clear cell renal cell carcinoma (ccRCC). We conducted a prospective, phase I trial of neoadjuvant nivolumab prior to nephrectomy in 15 evaluable patients with non-metastatic ccRCC. We leveraged tissue from that cohort to elucidate the effects of PD-1 inhibition on immune cell populations in ccRCC and correlate the evolving immune milieu with anti-PD-1 response. We found that nivolumab durably induces a pro-inflammatory state within the primary tumor, and baseline immune infiltration within the primary tumor correlates with nivolumab responsiveness. Nivolumab increases CTLA-4 expression in the primary tumor, and subsequent nephrectomy increases circulating concentrations of sPD-L1, sPD-L3 (sB7-H3), and s4-1BB. These findings form the basis to consider neoadjuvant immune checkpoint inhibition (ICI) for high-risk ccRCC while the tumor remains in situ and provide the rationale for perioperative strategies of novel ICI combinations.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Scientific reports - 14(2024), 1 vom: 17. Jan., Seite 1458 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Singla, Nirmish [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 18.01.2024 Date Revised 20.01.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41598-024-51889-9 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM367192810 |
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| 520 | |a Novel perioperative strategies are needed to reduce recurrence rates in patients undergoing nephrectomy for high-risk, non-metastatic clear cell renal cell carcinoma (ccRCC). We conducted a prospective, phase I trial of neoadjuvant nivolumab prior to nephrectomy in 15 evaluable patients with non-metastatic ccRCC. We leveraged tissue from that cohort to elucidate the effects of PD-1 inhibition on immune cell populations in ccRCC and correlate the evolving immune milieu with anti-PD-1 response. We found that nivolumab durably induces a pro-inflammatory state within the primary tumor, and baseline immune infiltration within the primary tumor correlates with nivolumab responsiveness. Nivolumab increases CTLA-4 expression in the primary tumor, and subsequent nephrectomy increases circulating concentrations of sPD-L1, sPD-L3 (sB7-H3), and s4-1BB. These findings form the basis to consider neoadjuvant immune checkpoint inhibition (ICI) for high-risk ccRCC while the tumor remains in situ and provide the rationale for perioperative strategies of novel ICI combinations | ||
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| 700 | 1 | |a Obradovic, Aleksandar Z |e verfasserin |4 aut | |
| 700 | 1 | |a Shenderov, Eugene |e verfasserin |4 aut | |
| 700 | 1 | |a Lombardo, Kara |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xiaopu |e verfasserin |4 aut | |
| 700 | 1 | |a Pons, Alice |e verfasserin |4 aut | |
| 700 | 1 | |a Zarif, Jelani C |e verfasserin |4 aut | |
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