Tumor infiltrating lymphocytes after neoadjuvant IRX-2 immunotherapy in oral squamous cell carcinoma: Interim findings from the INSPIRE trial
•Significant immune modulation was seen with neoadjuvant IRX-2 immunotherapy in this randomized, controlled clinical trial.•Increases in CD8 positive tumor infiltrating lymphocytes were the most prominent changes.•Greatest increases were seen in patients with p16 negative cancers. IRX-2 is a primary...
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Veröffentlicht in: | Oral oncology 2020-12, Vol.111, p.104928-104928, Article 104928 |
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Zusammenfassung: | •Significant immune modulation was seen with neoadjuvant IRX-2 immunotherapy in this randomized, controlled clinical trial.•Increases in CD8 positive tumor infiltrating lymphocytes were the most prominent changes.•Greatest increases were seen in patients with p16 negative cancers.
IRX-2 is a primary-cell-derived immune-restorative consisting of multiple human cytokines that act to overcome tumor-mediated immunosuppression and provide an in vivo tumor vaccination to increase tumor infiltrating lymphocytes (TILs). A randomized phase II trial was conducted of the IRX regimen 3 weeks prior to surgery consisting of an initial dose of cyclophosphamide followed by 10 days of regional perilymphatic IRX-2 cytokine injections and daily oral indomethacin, zinc and omeprazole (Regimen 1) compared to the identical regimen without IRX-2 cytokines (Regimen 2).
A total of 96 patients with previously untreated, stage II-IV oral cavity SCC were randomized 2:1 to experimental (1) or control (2) regimens (64:32). Paired biopsy and resection specimens from 62 patients were available for creation of tissue microarray (n = 39), and multiplex immunohistology (n = 54). Increases in CD8+ TIL infiltrate scores of at least 10 cells/mm2 were used to characterize immune responders (IR).
Regimen 1 was associated with significant increases in CD8+ infiltrates (p = 0.01) compared to Regimen 2. In p16 negative cancers (n = 26), significant increases in CD8+ and overall TILs were evident in Regimen 1 (p = 0.004, and 0.04 respectively). IRs were more frequent in Regimen 1 (74% vs 31%, p = 0.01). Multiplex immunohistology for PD-L1 expression confirmed an increase in PD-L1 H score for Regimen 1 compared to Regimen 2 (p = 0.11).
The findings demonstrate significant increases in TILs after perilymphatic IRX-2 injections. Three quarters of patients showed significant immune responses to IRX-2. (NCT 02609386). |
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ISSN: | 1368-8375 1879-0593 |
DOI: | 10.1016/j.oraloncology.2020.104928 |