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

Jiménez-Sánchez A1, Memon D2, Pourpe S3, Veeraraghavan H4, Li Y5, Vargas HA6, Gill MB1, Park KJ7, Zivanovic O8, Konner J9,Ricca J5, Zamarin D10, Walther T3, Aghajanian C9, Wolchok JD11, Sala E6, Merghoub T5, Snyder A12, Miller ML13.

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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.

https://www.ncbi.nlm.nih.gov/pubmed/28841418