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Immunosurveillance, which describes the immunologically mediated elimination of transformed cells, has been widely accepted in the context of bladder cancer for many decades with the successful use of Bacillus-Calmette Guerin for superficial bladder cancer since the 1970s. With the emergence of checkpoint inhibitor blockade in the treatment of urothelial cancers, there has been a resurgent interest in the immunology of bladder cancer. The theory of cancer immunoediting proposes that the immune system has both pro-tumorigenic and anti-tumor effects, the balance between the two determining the progression of an individual tumor. However, whilst there is evidence for the action of various immune cell populations in bladder cancer, a cohesive picture of the immune response to bladder cancer and its driving forces are still lacking. Additionally, little is still known about the normal immune landscape of the bladder. Future progress in bladder cancer therapeutic approaches will require a strong foundation in understanding the immunology of this disease. This review considers the evidence for the role of the main immune cell populations, both innate and adaptive, in the immune response to bladder cancer. Recent research and overarching themes in the immune response to bladder cancer are explored. The minimal evidence regarding the normal immune landscape of the human bladder is also summarized to contextualize downstream immune responses. Of specific interest are the innate and myeloid populations, some of which are resident in the human bladder and which have significant effects on downstream adaptive tumor immunity. We discuss factors which restrain the efficacy of populations known to have anti-tumor activity such as cytotoxic T cells, including the constraints on checkpoint blockade. Additionally, the effects on the immune response of tumor intrinsic factors such as the genomic subtype of bladder cancer and the effect of common therapies such as chemotherapy and intravesical Bacillus Calmette-Guerin are considered. A significant theme is the polarization of immune responses within the tumor by a heavily immunosuppressive tumor microenvironment which affects the phenotype of multiple innate and adaptive populations. Throughout, clinical implications are discussed with suggestions for future research directions and therapeutic targeting.

Background: There is insufficient evidence to support clinical decision-making for cancer patients diagnosed with COVID-19 due to the lack of large studies. Methods: We used data from a single large UK Cancer Center to assess the demographic/clinical characteristics of 156 cancer patients with a confirmed COVID-19 diagnosis between 29 February and 12 May 2020. Logistic/Cox proportional hazards models were used to identify which demographic and/or clinical characteristics were associated with COVID-19 severity/death. Results: 128 (82%) presented with mild/moderate COVID-19 and 28 (18%) with a severe case of the disease. An initial cancer diagnosis >24 months before COVID-19 [OR: 1.74 (95% CI: 0.71-4.26)], presenting with fever [6.21 (1.76-21.99)], dyspnea [2.60 (1.00-6.76)], gastro-intestinal symptoms [7.38 (2.71-20.16)], or higher levels of C-reactive protein [9.43 (0.73-121.12)] were linked with greater COVID-19 severity. During a median follow-up of 37 days, 34 patients had died of COVID-19 (22%). Being of Asian ethnicity [3.73 (1.28-10.91)], receiving palliative treatment [5.74 (1.15-28.79)], having an initial cancer diagnosis >24 months before [2.14 (1.04-4.44)], dyspnea [4.94 (1.99-12.25)], and increased CRP levels [10.35 (1.05-52.21)] were positively associated with COVID-19 death. An inverse association was observed with increased levels of albumin [0.04 (0.01-0.04)]. Conclusions: A longer-established diagnosis of cancer was associated with increased severity of infection as well as COVID-19 death, possibly reflecting the effects a more advanced malignant disease has on this infection. Asian ethnicity and palliative treatment were also associated with COVID-19 death in cancer patients.