Cancer Immunity Marker RNA Expression Levels Across Gynecologic Cancers - Implications for Immunotherapy

Q: What was the primary objective of this study?

To characterize cancer immunity marker expression in gynecologic cancers and compare immune landscapes between gynecologic tumor subtypes and non-gynecologic solid tumors.

Q: How were RNA expression levels quantified and categorized?

RNA expression levels of 51 cancer-immunity markers were ranked from 0-100 relative to a reference population and classified as low (0-24), moderate (25-74), or high (75-100).

Q: How did immune marker expression differ across gynecologic cancer sites?

Cervical cancer exhibited significantly higher expression rank levels for immune activating, pro-inflammatory, TIL markers, and checkpoints than uterine or ovarian cancer, while uterine and ovarian cancers showed no significant differences.

Sep 24, 2026

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Study characterizes cancer immunity marker RNA expression in gynecologic cancers and compares immune landscapes across tumor subtypes and non-gynecologic solid tumors. RNA expression levels of 51 cancer-immunity markers were measured in 72 patients, contrasted with a reference cohort of 735 control cancers, and stratified by ranked percentiles. Cervical cancer shows higher immune-activating, pro-inflammatory, TIL markers, and checkpoint expression than uterine or ovarian cancer, while uterine and ovarian profiles do not differ. Gynecologic tumors more often display high IDO-1, LAG3, and IL10, suggesting biomarker-informed trial directions.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages26

Reading Time1 h 6 min

AccessFree to download

Objective

Methods and Data Processing

Marker panel and reference cohort

Expression ranking and stratification

Results

Distribution by cancer site

Immune profile differences among gynecologic subtypes

PD-L1 association with pro-inflammatory markers

Comparison with non-gynecologic solid tumors

Clinical and Translational Implications

IDO-1 and LAG3 inhibitor rationale

Immunotherapy biomarkers and resistance context

“Immunogram” concept

Potential Impact on Research, Practice, Policy

Visualizing immune pressures for precision oncology

􀂦 Oregon Health and Sciences University of California, San Diego Moores Cancer Center Dartmouth Cancer Center Ben-Gurion University of the Negev [https://orcid.org/0000-0001-7265-3922](https://orcid.org/0000-0001-7265-3922) OmniSeq Inc OmniSeq Inc Omniseq OmniSeq Inc Ben Gurion University of the Negev University of California San Diego Moores Cancer Center University of California, San Diego Moores Cancer Center [https://orcid.org/0000-0003-41](https://orcid.org/0000-0003-41)10-1214 February 16th, 2023 [https://doi.org/10.21203/rs.3.rs-2551645/v1](https://doi.org/10.21203/rs.3.rs-2551645/v1) 􀁱 􀅏 This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License 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 pro¦les were identical according to expression rank (0-100) or rank level (low, moderate, or high) . Patients with cervical cancer had signi¦cantly higher expression level ranks of immune activating, proin§ammatory, tumor in¦ltrating lymphocyte markers and checkpoints than patients with uterine or ovarian cancer (p<0.001 for all comparisons) . However, there were no signi¦cant differences in immune marker expression between uterine and ovarian cancers. Tumors with PD-L1 TPS =>1% versus 0% had signi¦cantly higher expression levels of pro-in§ammatory 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. Gynecologic cancers have differential responses to immunotherapies, dependent on disease site and biomarkers. Immune checkpoint inhibitors are FDA approved in the frontline setting for cervical cancer patients who have PDL1 positive tumors, and for patients with recurrent endometrial cancer with tumors that are mismatch repair de¦cient or have high tumor mutational burdens. Despite these approvals, these biomarkers do not account for all tumor responses, and often lead to resistance. Furthermore, immunotherapies have not been found to be effective in patients with ovarian cancer. This raises the question of whether other immune mechanisms are at work within the tumor microenvironment that can enhance or hinder its response to immunotherapy. What this study adds: In this study, we found that patients with cervical cancer have signi¦cantly higher RNA expression levels of immune-activating, pro-in§ammatory and tumor in¦ltrating lymphocyte markers compared to patients with uterine or ovarian cancers. PDL1 positive tumors also have higher expression levels of pro in§ammatory markers compared to PDL1 negative tumors. Furthermore, gynecologic tumors have asigni¦cantly higher expression of IDO-1 markers, which are potentially actionable with IDO inhibitors. Though these ¦ ndings may begin to explain the success of immunotherapies with these particular characteristics, we do not yet know how to interpret RNA expression levels of both in§ammatory and inhibitory markers together. We therefore propose the concept of an “imm

FAQs

What was the primary objective of this study?

To characterize cancer immunity marker expression in gynecologic cancers and compare immune landscapes between gynecologic tumor subtypes and non-gynecologic solid tumors.

How were RNA expression levels quantified and categorized?

RNA expression levels of 51 cancer-immunity markers were ranked from 0-100 relative to a reference population and classified as low (0-24), moderate (25-74), or high (75-100).

How did immune marker expression differ across gynecologic cancer sites?

Cervical cancer exhibited significantly higher expression rank levels for immune activating, pro-inflammatory, TIL markers, and checkpoints than uterine or ovarian cancer, while uterine and ovarian cancers showed no significant differences.

Sep 24, 2026

Upload by acoobca