This case study examined the differential progression of primary tumor and several metastases during an off-treatment period in a heavily pretreated patient with high-grade serous ovarian cancer. Tumor progression/regression status correlated with T cell infiltration or exclusion, and T cell clonal expansion, but not with mutation burden or neoepitope number, indicating distinct tumor-immune microenvironments coexisting at different metastatic sites within the same patient. (Link to partially patient-produced VIDEO 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 ABSTRACT.
Author Info: (1) Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK. (2) Cancer Research UK Cambridge Institute, University
Author Info: (1) Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK. (2) Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK; European Molecular Biology Laboratory (EMBL), European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK. (3) Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. (4) Department of Medical Physics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. (5) Ludwig Collaborative/Swim Across America Laboratory, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. (6) Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. (7) Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK. (8) Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. (9) Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. (10) Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. (11) Ludwig Collaborative/Swim Across America Laboratory, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. (12) Ludwig Collaborative/Swim Across America Laboratory, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. (13) Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. (14) Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. (15) Ludwig Collaborative/Swim Across America Laboratory, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA; Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA; Department of Medicine, Weill Cornell Medical College, New York, NY, USA; Immunology and Microbial Pathogenesis Programs, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA. (16) Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. (17) Ludwig Collaborative/Swim Across America Laboratory, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. (18) Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA; Department of Medicine, Weill Cornell Medical College, New York, NY, USA. Electronic address: snyderca@mskcc.org. (19) Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK. Electronic address: martin.miller@cruk.cam.ac.uk.
