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

卵巢癌患者不同生长转移灶的异质性肿瘤免疫微环境

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作者: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

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 .

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