Immunotherapy of Bladder Cancer

Abstract

Bladder cancer used to be the only cancer treated by immunotherapy in form of intravesical BCG. Since approval of BCG for Non muscle invasive bladder cancer (NMIBC), there has been significant advancement in our knowledge about immune alteration in cancer and availability of immunotherapeutic agents. Tumor induced cell mediated immunosuppression is identified as a key factor for development and progression of cancer. Immune suppression in bladder cancer is predominantly through Macrophages. Myeloid derived suppressor cell, NK cells, Treg and expression of immune checkpoint receptor inhibitors also contribute to immune suppression. BCG induces innate immune response and its efficacy is limited to NMIBC. Novel immunotherapeutic agents evaluated in bladder cancer are administered locally or systemically to induce innate or adaptive immune response. Systemic administration of antibodies against PD-1/PD-L1 axis are now approved for treatment of locally advanced/metastatic bladder cancer as a first line as well as second line therapy. Pembrolizumab is also approved for BCG unresponsive NMIBC. Since response to immunotherapy are neither uniform nor universal, attempts are made to identify prognostic and predictive biomarkers. Identified biomarkers lack desired specificity and sensitivity. Several immune approaches using innate as well as adaptive mechanism are under evaluation to improve outcome of intravesical BCG or immune check point receptor inhibitors.