Cancer immunity marker RNA expression levels across gynecologic cancers: Implications for immunotherapy

Autor: Jessica Jou, Shumei Kato, Hirotaka Miyashita, Kartheeswaran Thangathurai, Sarabjot Pabla, Paul DePietro, Mary Nesline, Jeffrey Conroy, Eitan Rubin, Ramez Eskander, Razelle Kurzrock
Rok vydání: 2023
DOI: 10.21203/rs.3.rs-2551645/v1
Popis: 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 (p1% 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%, pConclusions: 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.
Databáze: OpenAIRE