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Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.01270

Immune Responses in Bladder Cancer-Role of Immune Cell Populations, Prognostic Factors and Therapeutic Implications

  • 1King's College London, United Kingdom
  • 2Guy's and St Thomas' NHS Foundation Trust, United Kingdom

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-tumourigenic and anti-tumour effects, the balance
between the two determining the progression of an individual tumour. 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
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 summarised to contextualise 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 tumour immunity. We
discuss factors which restrain the efficacy of populations known to have anti-tumour activity such as
cytotoxic T cells, including the constraints on checkpoint blockade. Additionally, the effects on the
immune response of tumour 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 tumour by a
heavily immunosuppressive tumour 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.

Keywords: immunosurveillance, Bladder cancer, genomic subtypes, Bacillus Calmette Guérin, Immunoediting

Received: 10 Aug 2019; Accepted: 04 Nov 2019.

Copyright: © 2019 Joseph and Enting. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Magdalene A. Joseph, King's College London, London, United Kingdom,