妇科癌症免疫标记RNA表达水平的差异:对免疫疗法的影响。
Cancer immunity marker RNA expression levels across gynecologic cancers: Implications for immunotherapy.
发表日期:2023 Aug 25
作者:
Jessica Jou, Shumei Kato, Hirotaka Miyashita, Kartheeswaran Thangathurai, Sarabjot Pabla, Paul DePietro, Mary K Nesline, Jeffrey M Conroy, Eitan Rubin, Ramez N Eskander, Razelle Kurzrock
来源:
Immunity & Ageing
摘要:
我们的目标是对妇科癌症中的免疫标记物表达进行特征描述,并比较不同妇科肿瘤亚型及非妇科实体肿瘤之间的免疫景观。我们对妇科癌症和非妇科癌症患者的51个癌症免疫标记物的RNA表达水平进行了分析,并将其与一个由735例对照癌症组成的参考人群进行了标准化。表达水平按照0-100进行排名,并分为低 (0-24)、中等 (25-74) 和高 (75-100) 百分位排名。在研究的72名患者中,43名 (60%) 患有卵巢癌,24名 (33%) 患有子宫癌,5名 (7%) 患有宫颈癌。根据表达排名 (0-100) 或排名水平 (低、中等、高),没有两个免疫概况是相同的。与子宫或卵巢癌患者相比,宫颈癌患者的免疫激活、促炎、肿瘤浸润淋巴细胞标记物和检查点的表达水平排名明显较高 (所有比较的p值<0.001)。然而,子宫癌和卵巢癌的免疫标记物表达没有显著差异。PD-L1 TPS≥1%与0%的肿瘤相比,存在明显更高比例的炎性标记物表达水平 (58% vs. 49%,p=0.0004)。与非妇科癌症患者相比,更多的妇科癌症患者表达高水平的IDO-1 (44% vs. 13%,p<0.001)、LAG3 (35% vs. 21%,p=0.008) 和IL10 (31% vs. 15%,p=0.002)。妇科癌症患者具有复杂和多样化的免疫景观,这些景观在个体之间以及与其他实体肿瘤之间存在差异。较高水平的IDO1和LAG3提示妇科癌症可能需要开展IDO1抑制剂或LAG3抑制剂的临床试验。
Our objective was to characterize cancer immunity marker expression in gynecologic cancers and compare immune landscapes between gynecologic tumor subtypes and with non-gynecologic solid tumors. RNA expression levels of 51 cancer-immunity markers were analyzed in patients with gynecologic cancers vs. non-gynecologic cancers, and normalized to a reference population of 735 control cancers, ranked from 0-100, and categorized as low (0-24), moderate (25-74), or high (75-100) percentile rank. Of the 72 patients studied, 43 (60%) had ovarian, 24 (33%) uterine, and 5 (7%) cervical cancer. No two immune profiles were identical according to expression rank (0-100) or rank level (low, moderate, or high). Patients with cervical cancer had significantly higher expression level ranks of immune activating, pro-inflammatory, tumor infiltrating lymphocyte markers and checkpoints than patients with uterine or ovarian cancer (p<0.001 for all comparisons). However, there were no significant differences in immune marker expression between uterine and ovarian cancers. Tumors with PD-L1 TPS =>1% versus 0% had significantly higher expression levels of pro-inflammatory markers (58 vs. 49%, p=0.0004). Compared to patients with non-gynecologic cancers, more patients with gynecologic cancers express high levels of IDO-1 (44 vs. 13%, p<0.001), LAG3 (35 vs. 21%, p=0.008) and IL10 (31 vs. 15%, p=0.002.) Patients with gynecologic cancers have complex and heterogeneous immune landscapes that are distinct from patient to patient and from other solid tumors. High levels of IDO1 and LAG3 suggest that clinical trials with IDO1 inhibitors or LAG3 inhibitors, respectively, may be warranted in gynecologic cancers.