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

Publication date: 24 August 2017
Source:Cell, Volume 170, Issue 5
Author(s): Alejandro Jiménez-Sánchez, Danish Memon, Stephane Pourpe, Harini Veeraraghavan, Yanyun Li, Hebert Alberto Vargas, Michael B. Gill, Kay J. Park, Oliver Zivanovic, Jason Konner, Jacob Ricca, Dmitriy Zamarin, Tyler Walther, Carol Aghajanian, Jedd D. Wolchok, Evis Sala, Taha Merghoub, Alexandra Snyder, Martin L. Miller
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

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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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