IBCN 2017: Urologist-Led Success Stories in Stewardship of Imaging for Bladder Cancer

Lisbon, Portugal (UroToday.com) This session focused on bladder tumor immunology including genetics and response to treatments. Randy Sweis from The University of Chicago presented his work regarding the genome analysis of bladder cancer immunophenotypes. The used The Cancer Genome Atlas (TCGA) to define a bladder cancer cohort and immunophenotypes by gene expression profiling across multiple datasets of muscle invasive bladder cancer (MIBC). Immune gene signature is associated with CD8+ cell infiltration by IHC but not mutational density. T cell-inflamed tumors have higher expression of immune inhibitory markers and most immune checkpoint targets show concordant expression. The non-inflamed T cell tumors have a unique profile with beta-catenin and PPAR-gamma. FGFR3 alterations are unique to no T-cell inflamed tumors and expression correlates with lack of T cells. In conclusion, we have improved understanding and characterization of immune response according to expression profiling.

John Rodriguez-Faba from Mount Sinai, New York, New York discussed immune system profiling and bladder cancer. Immunotherapies including BCG and immune checkpoint inhibitors improved our understanding of the role of the immune system and bladder cancer. In his work, they performed immune profiling where bladder cancer decreases the number of both peripheral and tumor-resident NK and T cells and induces peripheral NK cell maturation. Moreover, bladder cancer imprints a phenotype of exhaustion on NK and T cells defined by upregulation of Tim-3, TIGIT and PD-1 detectable in tumor and peripheral blood from bladder cancer patients. In conclusion the peripheral immune system may be important biomarker and regulator for bladder cancer and further research needed in this arena.

Colin PN Dinney from MD Anderson, Houston, TX discussed current gene-therapy modalities in bladder cancer. SUO-CTC phase II trial was completed and noted a 35% recurrence free survival with acceptable toxicity using the Ad-IFN-syn3 recombinant gene therapy for patients with non-muscle invasive bladder cancer. Anti-PDL1 antibodies prolongs survival in Poly IC treated mice with melanoma setting up rational for other cancer sites as well. Local in vivo IFN-alpha induction by Poly IC slows tumor growth and improved survival in these mice. Immune response mediated by Poly IC requires an intact IRN-alpha receptor and induces but not independent of IL-15. There appears an innate and adaptive immune response to Poly IC. Studies are underway assessing the lentiviral recombinant vector which has shown upregulation of PDL1 in mice. There is a trial with immune checkpoint inhibitors and gene therapy underway.

Speaker(s): Randy Sweis, The University of Chicago; John Rodriguez-Faba, Mount Sinai, New York, New York; Colin PN Dinney, MD Anderson, Houston, TX

Written by: Stephen B. Williams, M.D., Associate Professor, Division of Urology, The University of Texas Medical Branch, Galveston, TX. and Ashish M. Kamat, M.D. Professor, Department of Urology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX., at the International Bladder Cancer Network - October 21, 2017- Lisbon, Portugal

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