Jou Jessica, Kato Shumei, Miyashita Hirotaka, Thangathurai Kartheeswaran, Pabla Sarabjot, DePietro Paul, Nesline Mary, Conroy Jeffrey, Rubin Eitan, Eskander Ramez, Kurzrock Razelle
Oregon Health and Sciences.
University of California, San Diego Moores Cancer Center.
Res Sq. 2023 Feb 16:rs.3.rs-2551645. doi: 10.21203/rs.3.rs-2551645/v1.
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.
我们的目标是描述妇科癌症中癌症免疫标志物的表达情况，并比较妇科肿瘤亚型之间以及与非妇科实体瘤之间的免疫格局。分析了妇科癌症患者与非妇科癌症患者中51种癌症免疫标志物的RNA表达水平，并将其与735例对照癌症的参考人群进行标准化，范围为0至100，并分为低（0至24）、中（25至74）或高（75至100）百分位数等级。在研究的72例患者中，43例（60%）患有卵巢癌，24例（33%）患有子宫癌，5例（7%）患有宫颈癌。根据表达等级（0至100）或等级水平（低、中或高），没有两种免疫图谱是相同的。宫颈癌患者的免疫激活、促炎、肿瘤浸润淋巴细胞标志物和检查点的表达水平等级显著高于子宫癌或卵巢癌患者（所有比较p<0.001）。然而，子宫癌和卵巢癌之间的免疫标志物表达没有显著差异。PD-L1 TPS =>1%与0%的肿瘤相比，促炎标志物的表达水平显著更高（58%对49%，p = 0.0004）。与非妇科癌症患者相比，更多的妇科癌症患者高水平表达IDO-1（44%对13%，p<0.001）、LAG3（35%对21%，p = 0.008）和IL10（31%对15%，p = 0.002）。妇科癌症患者具有复杂且异质的免疫格局，患者之间以及与其他实体瘤不同。高水平的IDO1和LAG3表明，分别使用IDO1抑制剂或LAG3抑制剂进行临床试验在妇科癌症中可能是必要的。
