Heterogeneous Tumor-Immune Microenvironments among Differentially Growing Metastases in an Ovarian Cancer Patient.
Vargas, Hebert Alberto
Gill, Michael B
Park, Kay J
Wolchok, Jedd D
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Jiménez-Sánchez, A., Memon, D., Pourpe, S., Veeraraghavan, H., Li, Y., Vargas, H. A., Gill, M. B., et al. (2017). Heterogeneous Tumor-Immune Microenvironments among Differentially Growing Metastases in an Ovarian Cancer Patient.. Cell, 170 927-938.e20. https://doi.org/10.1016/j.cell.2017.07.025
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.
T-Lymphocytes, Humans, Cystadenocarcinoma, Serous, Ovarian Neoplasms, Neoplasm Metastasis, Antigens, Neoplasm, Gene Expression Regulation, Neoplastic, Mutation, Female, Tumor Microenvironment, Transcriptome
Cancer Research UK core grant (C14303/A17197), Memorial Sloan Kettering Cancer Cencter core grant (P30 CA008748)
Cancer Research UK (C14303/A17197)
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External DOI: https://doi.org/10.1016/j.cell.2017.07.025
This record's URL: https://www.repository.cam.ac.uk/handle/1810/265703
Attribution 4.0 International
Licence URL: http://creativecommons.org/licenses/by/4.0/