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Jiménez-Sánchez, Alejandro; Memon, Danish; Pourpe, Stephane; Veeraraghavan, Harini; Li, Yanyun; Vargas, Hebert Alberto; Gill, Michael B.; Park, Kay J.; Zivanovic, Oliver; Konner, Jason; Ricca, Jacob; Zamarin, Dmitriy; Walther, Tyler; Aghajanian, Carol; Wolchok, Jedd D.; Sala, Evis; Merghoub, Taha; Snyder, Alexandra; Miller, Martin L.
Cell, 08/2017, Volume: 170, Issue: 5Journal Article
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. Display omitted Display omitted •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.
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