Exploratory evaluation of the somatic and immunologic landscape of primary and metastatic cervical cancer to better inform future clinical trial development
Recommended Citation
Cerda V, Rimel BJ, Mercer J, et al. Exploratory evaluation of the somatic and immunologic landscape of primary and metastatic cervical cancer to better inform future clinical trial development. International Journal of Gynecological Cancer. 2025:102677. doi:10.1016/j.ijgc.2025.102677
Abstract
Objective: To explore the somatic and immunologic landscape of cervical primary vs metastatic tumors for differential sensitivity of metastatic cervical sites and potential therapeutic implications.
Methods: Patients with sequenced squamous cell cervical cancer were selected from the Tempus Database (2016-2023). The cohort included 136 unmatched samples (73 primary, 63 metastatic sites). Pathogenic somatic mutations and gene expression patterns of immune cells were evaluated for relative intra-tumor abundance. Immune cell percentages, tumor mutational burden (TUMOR MUTATIONAL BURDEN), and tumor neoantigen burden (TUMOR NEOANTIGEN BURDEN) were compared across tumor sites. Chi-squared/Fischer’s exact tests or Kruskal-Wallis tests were used to assess statistical significance.
Results: The median cohort age was 52 years (IQR 42, 60). High tumor mutational burden (≥ 10 mut/Mb) was seen in 9.6% (9% primary, 0% lung, 17% liver, 17% lymph node, p=0.7) of patients. High MSI was noted in 1.5% (p=0.7) of patients. PD-L1 status was positive in 78% (76% primary, 88% lung, 71% liver, and 80% lymph node, p=0.8) of patients. Median tumor neoantigen burden was 1.71 (IQR 0.98, 3.20). Liver lesions had the lowest percentage of B cells (p=0.001) and a higher percentage of macrophages (p=0.053) versus other sites. There was a trend towards lower percentages of CD4 cells (p=0.053) and NK cells (p=0.090) in lymph nodes versus other sites. PIK3CA was the most common pathogenic somatic alteration, but not statistically different across sites (q=0.9).
Conclusions: Molecular and immune profiling of primary and metastatic lesions indicated that liver lesions had a less immunogenic microenvironment. Further interrogation of the molecular landscape across paired samples is needed to better inform the development and use of novel therapies.
Document Type
Article
PubMed ID
41138573