Michigan Medicine, University of Michigan, Ann Arbor, MI 48109, United States.
Michigan Medicine, University of Michigan, Ann Arbor, MI 48109, United States.
Oral Oncol. 2020 Dec;111:104928. doi: 10.1016/j.oraloncology.2020.104928. Epub 2020 Jul 29.
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/mm 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. (NCT02609386).
IRX-2 是一种源自原代细胞的免疫修复因子，包含多种细胞因子，可作用于克服肿瘤介导的免疫抑制，提供体内肿瘤疫苗接种以增加肿瘤浸润淋巴细胞 (TIL)。进行了一项随机的 II 期试验，比较了手术前 3 周接受 IRX 方案治疗的患者（初始剂量为环磷酰胺，随后进行 10 天的局部周围淋巴 IRX-2 细胞因子注射和每日口服吲哚美辛、锌和奥美拉唑[方案 1]）与未接受 IRX-2 细胞因子治疗的患者（方案 2）。
共招募了 96 名未经治疗的 II-IV 期口腔鳞状细胞癌患者，按照 2:1 的比例随机分配至实验组 (1) 或对照组 (2) 方案 (64:32)。对 62 名患者的配对活检和切除标本进行了组织微阵列 (n=39) 和多重免疫组化 (n=54) 分析。CD8+TIL 浸润评分至少增加 10 个细胞/mm2 用于鉴定免疫应答者 (IR)。
与对照组相比，方案 1 显著增加了 CD8+浸润 (p=0.01)。在 p16 阴性癌症患者 (n=26) 中，方案 1 中明显增加了 CD8+和总体 TIL 浸润 (p=0.004 和 0.04)。方案 1 中的 IR 更为常见 (74% vs 31%，p=0.01)。PD-L1 表达的多重免疫组化分析证实，与对照组相比，方案 1 中 PD-L1 H 评分增加 (p=0.11)。
这些发现表明，周围淋巴 IRX-2 注射后 TIL 明显增加。四分之三的患者对 IRX-2 有明显的免疫反应。(NCT02609386)。
