학술논문
Cancer immunity marker RNA expression levels across gynecologic cancers: Implications for immunotherapy.
Document Type
Author
Jou J; Oregon Health and Sciences.; Kato S; University of California, San Diego Moores Cancer Center.; Miyashita H; Dartmouth Cancer Center.; Thangathurai K; Ben-Gurion University of the Negev.; Pabla S; OmniSeq Inc.; DePietro P; OmniSeq Inc.; Nesline M; Omniseq.; Conroy J; OmniSeq Inc.; Rubin E; Ben Gurion University of the Negev.; Eskander R; University of California San Diego Moores Cancer Center.; Kurzrock R; University of California, San Diego Moores Cancer Center.
Source
Country of Publication: United States NLM ID: 101768035 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: Res Sq Subsets: PubMed not MEDLINE
Subject
Language
English
Abstract
Background: 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. Methods: 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. Results: 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.) Conclusions: 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.