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

Cell. 2017 Aug 24;170(5):927-938.e20. doi: 10.1016/j.cell.2017.07.025.

Abstract

We present an exceptional case of a patient with high-grade serous ovarian cancer, treated with multiple chemotherapy regimens, who exhibited regression of some metastatic lesions with concomitant progression of other lesions during a treatment-free period. Using immunogenomic approaches, we found that progressing metastases were characterized by immune cell exclusion, whereas regressing and stable metastases were infiltrated by CD8+ and CD4+ T cells and exhibited oligoclonal expansion of specific T cell subsets. We also detected CD8+ T cell reactivity against predicted neoepitopes after isolation of cells from a blood sample taken almost 3 years after the tumors were resected. These findings suggest that multiple distinct tumor immune microenvironments co-exist within a single individual and may explain in part the heterogeneous fates of metastatic lesions often observed in the clinic post-therapy. VIDEO ABSTRACT.

Publication types

  • Case Reports

MeSH terms

  • Antigens, Neoplasm / immunology
  • Cystadenocarcinoma, Serous / genetics
  • Cystadenocarcinoma, Serous / immunology
  • Cystadenocarcinoma, Serous / pathology*
  • Cystadenocarcinoma, Serous / therapy
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mutation
  • Neoplasm Metastasis / genetics
  • Neoplasm Metastasis / immunology*
  • Neoplasm Metastasis / therapy
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / pathology*
  • Ovarian Neoplasms / therapy
  • T-Lymphocytes / immunology
  • Transcriptome
  • Tumor Microenvironment*

Substances

  • Antigens, Neoplasm