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.
Differential progression of metastases during off-treatment period.
Coexistence of distinct tumor-immune microenvironments within the same individual.
Tumor regression and progression correlated with T cell infiltration and exclusion.
Clonal neoepitopes elicited reactivity of circulating CD8 + T cells.
Distinct tumor immune microenvironments co-exist within a single individual and may help to explain the heterogeneous fates of metastatic lesions often observed post-therapy.