Division of Gynecologic Oncology, Oregon Health and Sciences University, Knight Cancer Institute, Portland, Oregon.
Division of Hematology & Oncology and Center for Personalized Cancer Therapy, University of California San Diego, Moores Cancer Center, La Jolla, California.
Mol Cancer Ther. 2023 Nov 1;22(11):1352-1362. doi: 10.1158/1535-7163.MCT-23-0270.
Our objective was to characterize cancer-immunity marker expression in gynecologic cancers and compare immune landscapes between gynecologic tumor subtypes and with nongynecologic solid tumors. RNA expression levels of 51 cancer-immunity markers were analyzed in patients with gynecologic cancers versus nongynecologic cancers, and normalized to a reference population of 735 control cancers, ranked from 0 to 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, proinflammatory, 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 tumor proportional score (TPS) ≥1% versus 0% had significantly higher expression levels of proinflammatory markers (58 vs. 49%, P = 0.0004). Compared to patients with nongynecologic 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的癌症免疫标志物表达，并比较妇科肿瘤亚型与非妇科实体瘤之间的免疫图谱。分析了妇科癌症患者与非妇科癌症患者的 51 种癌症免疫标志物的 RNA 表达水平，并与 735 例对照癌症的参考人群进行了归一化，这些对照癌症的表达水平从 0 到 100 进行了排名，并分为低（0-24）、中（25-74）或高（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）或排名级别（低、中或高），没有两个免疫谱是相同的。与子宫癌或卵巢癌患者相比，宫颈癌患者的免疫激活、促炎、肿瘤浸润淋巴细胞标志物和检查点的表达水平明显更高（所有比较均 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 肿瘤比例评分（TPS）≥1%与 0%的肿瘤具有更高水平的促炎标志物（58%比 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%比 13%，P<0.001）、LAG3（35%比 21%，P=0.008）和 IL10（31%比 15%，P=0.002）。妇科癌症患者具有复杂而异质的免疫图谱，在患者之间和与其他实体瘤之间均存在差异。高水平的 IDO1 和 LAG3 表明，分别在妇科癌症中进行 IDO1 抑制剂或 LAG3 抑制剂的临床试验可能是合理的。
