PMC9661726_01
Sequential CT scans showing a response to pemprolizumab. (A) A large bladder tumor that was biopsied prior to starting pembrolizumab immunotherapy with a complete response in the bladder. (B) Multiple lung metastases from bladder cancer that obtained a complete response with pembrolizumab immunotherapy. (C) Multiple hepatic metastases from bladder cancer that obtained a complete response with pembrolizumab immunotherapy.
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A second CT scan in January 2015 showed a large bladder tumor and metastases in the lung and liver ( Figure 1A ;  Supplementary Figure S1 ). She was offered standard-of-care treatment, vinflunine, in her city, but elected to participate in an ongoing clinical study in Rome, Italy ( Supplementary Figure S1 ). Sequential CT scans revealed a rapid reduction of the tumors in all three regions ( Figure 1 ). Serial CT scans showed that she has been free of all disease and off of therapy for over 6 years ( Figure 1 ;  Supplementary Figure S1 ).
Histopathological assessment of the patient's bladder urothelial carcinoma. (A) Micropapillary histopathology was observed by H&E staining. (B) PD-L1 expression was assessed by immunohistochemistry.
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Immunohistochemistry (IHC) demonstrated 15% of PD-L1 expression (DAKO 22C3) ( Figure 2 ).
Summary of the patient's major findings using the MF Portrait9 and integrative genomic and transcriptomic analysis (Data Supplement). (A) A planetary schematic representation of the molecular and functional characteristics of the patient's tumor. Blue represents anti-tumor activity (immune active microenvironment) and red represents pro-tumor activity (immune suppressive microenvironment, angiogenesis, tumor stroma). The size of the dot corresponds to the strength of the presented gene signatures. (B) List of key findings using WES and RNA-seq analysis represented as NGS and RNA-seq, respectively.
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BostonGene Tumor Portrait  Test, a comprehensive genomic and transcriptomic analysis using whole-exome sequencing (WES) and RNA sequencing (RNA-seq), was performed to understand the mechanisms of response to immunotherapy. Based on transcriptomic profiling and the TME subtype represented as the MF Portrait in this test, the patient's tumor can be described as an "Immune Desert", which is usually characterized by a non-inflamed TME and a high tumor proliferation rate ( Figure 3 ). ATM mutation in homologous recombination genes. A summary of the patient's findings is shown in  Figure 3 .