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

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.