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

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Jiménez-Sánchez, Alejandro 
Memon, Danish 
Pourpe, Stephane 
Veeraraghavan, Harini 
Li, Yanyun 


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.



Antigens, Neoplasm, Cystadenocarcinoma, Serous, Female, Gene Expression Regulation, Neoplastic, Humans, Mutation, Neoplasm Metastasis, Ovarian Neoplasms, T-Lymphocytes, Transcriptome, Tumor Microenvironment

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Elsevier BV
Cancer Research UK (C14303/A17197)
Cancer Research UK (20879)
Cancer Research UK (22905)
Cancer Research UK (15871)
Cancer Research UK (15973)
Cancer Research UK (15601)
Cancer Research UK core grant (C14303/A17197), Memorial Sloan Kettering Cancer Cencter core grant (P30 CA008748)