1. Nalley, Catlin

Article Content

A recent analysis suggests that further investigation of transcriptomic immune profiling is warranted to better predict which cervical cancer patients may benefit most from immunotherapy.

Cervical Cancer. Cer... - Click to enlarge in new windowCervical Cancer. Cervical Cancer

The abstract, "Transcriptomic immune profiling: A precision path forward for immunotherapy in patients with cervical cancer?" was presented during the Society of Gynecologic Oncology 2021 Virtual Annual Meeting.


"Immunotherapy has emerged as a promising intervention in metastatic and recurrent cervical cancer; however, response rates to single agents have been modest, although there have been some durable responses," noted John J. Wallbillich, MD, Assistant Professor of Clinical Gynecologic Oncology at Wayne State University.


"As far as the next step in a precision approach to improving outcomes for immunotherapy, we are interested in transcriptomic immune profiling, which is a relatively new approach to assessing immune cell content and/or pathways in a tumor."

John J. Wallbillich,... - Click to enlarge in new windowJohn J. Wallbillich, MD. John J. Wallbillich, MD

This approach uses RNA profiling of all-or many-genes expressed by a tumor and has potential to serve as a basis for more robust biomarkers for immunotherapy, according to Wallbillich, who is also a member of the Gynecologic Oncology team at Karmanos Cancer Institute in Detroit.


"In the case of cervical cancer, transcriptomic immune profiling studies have been limited to newly diagnosed, mostly early-stage cases," he explained. "We, therefore, sought to use transcriptomic immune profiling to develop a more representative analysis of the cervical cancer population receiving immunotherapy."


The researchers utilized a multi-omic approach to analyze cervical cancer tumor samples, which included next-generation sequencing, whole exome sequencing, immunohistochemistry, and whole transcriptome sequencing.


Specific markers of interest included PD-L1, microsatellite instability, and tumor mutational burden (TMB). "Of note, HPV status was included as a variable using a proxy indicator, specifically TP53 mutations," said Wallbillich. "Specific to transcriptomic immune profiling, immune cell infiltration and quantification were calculated via quanTIseq. Enrichment analysis was used to analyze for immune pathways."


The investigators used chi-square test and Wilcoxon rank sum test to determine statistical significance, which was adjusted for multiple comparisons using Benjamini & Hochberg and Bonferroni, respectively. The researchers set the statistical significance at a threshold of adjusted p-value < 0.01.


From 2008 to 2020, 930 patients with cervical cancer underwent profiling. They had a median age of 52 years and 449 (48.3%) had metastatic disease.


Among the FDA-approved companion markers of response to immunotherapy, the most commonly present was PD-L1+ (83.5%), according to Wallbillich. "Compared to adenocarcinoma, squamous cell carcinoma had a more robust immune signal with increased PD-L1+, TMB-high, infiltration of multiple types of immune cells (neutrophils, CD8+ T cells, regulatory T cells), and expression of multiple immune checkpoint genes."


The researchers reported that PD-L1+ status was also significantly associated with increased infiltration of multiple immune cells, including macrophage M1 (3.51% vs. 2.04%), NK (2.6% vs. 3.2%), CD8+ T (0.7% vs. 0%), and regulatory T (2.4% vs. 1.3%) cell infiltration. TMB-high was associated with increased infiltration of neutrophils and CD8+ T cells as was older age, noted Wallbillich.


Older patients over the age of 63 years had significantly "more somatic TP53 mutations (25.2% vs. 10.1%, indicating more non-HPV tumors with increasing age) and increased dendritic cell infiltration compared to younger patients," according to the study authors.


"In conclusion, cervical squamous cell carcinoma had a higher immune signal than adenocarcinoma, including increased immunotherapy biomarkers, such as PD-L1 and tumor mutational burden, increased immune cell infiltration, and upregulated immune checkpoint genes," he said. "Non-HPV status and dendritic cell infiltration increased with advanced age.


"We believe these results suggest that transcriptomic immune profiling should be further investigated in future predictive biomarker development for immunotherapy in patients with cervical cancer," Wallbillich concluded.


Catlin Nalley is a contributing writer.


More Articles on Gynecologic Cancer

You can find additional research and treatments for gynecologic cancer at the Oncology Times online collection. Check out the many articles and resources here: