Using cancer-immunity marker RNA expression levels to compare immunograms across gynecologic cancers (049)

Abstract

Objectives: To describe the immune microenvironment in gynecologic cancers using RNA expression of numerous cancer-immunity markers. Methods: Cancer-immunity markers among 72 eligible, consecutive patients with gynecologic cancers seen at the University of California, San Diego Center for Personalized Cancer Therapy, were examined using the Omniseq platform. Tumor tissues were extracted for RNA and sequenced. RNA expression of 51 immune markers, including checkpoint markers (n=9 markers including PD-L1, PD-L2, CTLA-4, and LAG3), macrophage-associated markers (n=5 markers including CCR2, CD68, and CSF1R), immune escape/anti-inflammatory response markers (n=5 markers including ADORA2A, IDO1), T cell primed markers (n=15 markers including CD40 and ICOS), tumor-infiltrating lymphocyte markers (n=8 markers including CD4, CD8, and FOXP3) and pro-inflammatory markers (n=2 markers including IL1B and TNF) were seen. Expression levels were normalized to an internal reference of 735 diverse tumor samples and ranked from 0-100. Rank values were set on a scale of 1 to 100 and stratified into “High” (75 - 100), “Moderate” (26-74), and “Low” (0-25). Immune marker expression ranks were compared between patients with gynecologic cancers and those with non-gynecologic cancers. Immune marker expression ranks were averaged for each gynecologic disease site and graphed to obtain an “immunogram.” Conclusions: Continued examination of cancer immunograms may help describe important immunologic characteristics of gynecologic cancers and distinguish them from other solid tumors, potentially informing novel treatment approaches. For example, the preferentially high IDO1 expression in gynecologic cancers may suggest that new drugs, such as IDO1 inhibitors should undergo clinical trials in gynecologic cancers. Furthermore, no two patients in the 72-patient cohort exhibited the same immunogram, highlighting the potential need for precision immunotherapy combinatorial approaches and supporting novel clinical trial designs in this space. Objectives: To describe the immune microenvironment in gynecologic cancers using RNA expression of numerous cancer-immunity markers. Methods: Cancer-immunity markers among 72 eligible, consecutive patients with gynecologic cancers seen at the University of California, San Diego Center for Personalized Cancer Therapy, were examined using the Omniseq platform. Tumor tissues were extracted for RNA and sequenced. RNA expression of 51 immune markers, including checkpoint markers (n=9 markers including PD-L1, PD-L2, CTLA-4, and LAG3), macrophage-associated markers (n=5 markers including CCR2, CD68, and CSF1R), immune escape/anti-inflammatory response markers (n=5 markers including ADORA2A, IDO1), T cell primed markers (n=15 markers including CD40 and ICOS), tumor-infiltrating lymphocyte markers (n=8 markers including CD4, CD8, and FOXP3) and pro-inflammatory markers (n=2 markers including IL1B and TNF) were seen. Expression levels were normalized to an internal reference of 735 diverse tumor samples and ranked from 0-100. Rank values were set on a scale of 1 to 100 and stratified into “High” (75 - 100), “Moderate” (26-74), and “Low” (0-25). Immune marker expression ranks were compared between patients with gynecologic cancers and those with non-gynecologic cancers. Immune marker expression ranks were averaged for each gynecologic disease site and graphed to obtain an “immunogram.” Conclusions: Continued examination of cancer immunograms may help describe important immunologic characteristics of gynecologic cancers and distinguish them from other solid tumors, potentially informing novel treatment approaches. For example, the preferentially high IDO1 expression in gynecologic cancers may suggest that new drugs, such as IDO1 inhibitors should undergo clinical trials in gynecologic cancers. Furthermore, no two patients in the 72-patient cohort exhibited the same immunogram, highlighting the potential need for precision immunotherapy combinatorial approaches and supporting novel clinical trial designs in this space.