Heterogeneous Tumor-Immune Microenvironments among Differentially Growing Metastases in an Ovarian Cancer Patient

Area of Science:

• Oncology
• Immunology
• Genomics

Background:

• High-grade serous ovarian cancer (HGSOC) is often treated with multiple chemotherapy regimens.
• Metastatic lesions can exhibit heterogeneous responses to therapy, with some progressing while others regress.

Observation:

• A patient with HGSOC showed regression of some metastatic lesions and progression of others during a treatment-free period.
• Immunogenomic analysis was performed on tumor samples and blood.

Findings:

• Progressing metastases were characterized by immune cell exclusion.
• Regressing and stable metastases were infiltrated by CD8+ and CD4+ T cells, showing oligoclonal expansion.
• CD8+ T cell reactivity against predicted neoepitopes was detected years after tumor resection.

Implications:

• Distinct tumor immune microenvironments can coexist within an individual.
• This coexistence may explain the heterogeneous clinical outcomes of metastatic lesions post-therapy.
• Understanding these microenvironments could inform future treatment strategies for ovarian cancer.