Cell
Volume 170, Issue 5, 24 August 2017, Pages 927-938.e20
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Article
Heterogeneous Tumor-Immune Microenvironments among Differentially Growing Metastases in an Ovarian Cancer Patient

https://doi.org/10.1016/j.cell.2017.07.025Get rights and content
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Highlights

  • 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.

Summary

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.

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