Mechanisms of BCG immunotherapy and its outlook for bladder cancer

  title={Mechanisms of BCG immunotherapy and its outlook for bladder cancer},
  author={Caroline Pettenati and Molly A. Ingersoll},
  journal={Nature Reviews Urology},
BCG immunotherapy is the gold-standard treatment for non-muscle-invasive bladder cancer at high risk of recurrence or progression. Preclinical and clinical studies have revealed that a robust inflammatory response to BCG involves several steps: attachment of BCG; internalization of BCG into resident immune cells, normal cells, and tumour urothelial cells; BCG-mediated induction of innate immunity, which is orchestrated by a cellular and cytokine milieu; and BCG-mediated initiation of tumour… 
Trained immunity as a molecular mechanism for BCG immunotherapy in bladder cancer
It is proposed that trained immunity could be one of the important mechanisms mediating BCG immunotherapy and could contribute to a personalized approach to BCG therapy in patients with bladder cancer.
Bacillus Calmette–Guérin immunotherapy for bladder cancer: a review of immunological aspects, clinical effects and BCG infections
The current knowledge of how BCG immunity is induced is described, from internalization of BCG bacilli in urothelial cells, to cytokine‐ and chemokine‐mediated recruitment of neutrophils, monocytes, macrophages, T cells, B cells and natural killer cells.
Bladder cancer, a unique model to understand cancer immunity and develop immunotherapy approaches
The potential of using bladder cancer as a model to investigate cancer immune response mechanisms and new therapeutic approaches, which may be translated into immunotherapy of other human cancers, is explored.
Evolution of immunotherapy in the treatment of non-muscle-invasive bladder cancer
An overview of the evolution of immunotherapy for NMIBC is provided, beginning from the original immunotherapy-BCG – to current agents including checkpoint inhibitors, IL-15 agonists, viral gene therapies and therapeutic cancer vaccines.
Immune Responses in Bladder Cancer-Role of Immune Cell Populations, Prognostic Factors and Therapeutic Implications
The evidence for the role of the main immune cell populations, both innate and adaptive, in the immune response to bladder cancer are considered and a significant theme is the polarization of immune responses within the tumor by a heavily immunosuppressive tumor microenvironment.
Genomic Biomarkers and Underlying Mechanism of Benefit from BCG Immunotherapy in Non-Muscle Invasive Bladder Cancer
In this cohort, improved outcomes after BCG immunotherapy were observed in patients with high TMB, high NAL and deleterious mutations in DDR genes, suggesting BCG may induce tumor-specific immune response by enhancing the recognition of neoantigens.
Bacterial immunotherapy for cancer induces CD4-dependent tumor-specific immunity through tumor-intrinsic interferon-γ signaling
It is established that a bacterial immunotherapy for cancer is capable of inducing tumor immunity, an antitumor effect that results from enhanced function of tumor-specific CD4 T cells, and ultimately requires tumor-intrinsic IFN-γ signaling, via a mechanism that is distinct from other tumor immunotherapies.
Recombinant BCG overexpressing a STING agonist elicits trained immunity and improved antitumor efficacy in non-muscle invasive bladder cancer
It is demonstrated that the antitumor efficacy of BCG during bladder cancer is mediated via myeloid cell “training” in which BCG leads to epigenetic modifications accompanied by metabolic and cellular reprogramming changes which promote antitumors immunity.
Mechanisms of immune evasion in bladder cancer
The major mechanisms of immune evasion in bladder cancer are discussed and novel pathways and molecular targets that may help to attenuate tumor-induced immune tolerance, overcome resistance to immunotherapy and improve clinical outcomes are highlighted.


Preexisting BCG-Specific T Cells Improve Intravesical Immunotherapy for Bladder Cancer
New insight is provided into the mechanisms behind BCG’s success in the bladder and it is suggested that parenteral BCG exposure may boost the success rate for bladder cancer treatment, and monitoring patients’ response to purified protein derivative may provide a simple strategy that could improve therapeutic response.
Role of urothelial cells in BCG immunotherapy for superficial bladder cancer
Intravesical instillation of Bacillus Calmette-Guérin (BCG) is used for the treatment of superficial bladder cancer, both to reduce the recurrence rate of bladder tumour and to diminish the risk of
Systemic Immunotherapy of Non-Muscle Invasive Mouse Bladder Cancer with Avelumab, an Anti–PD-L1 Immune Checkpoint Inhibitor
In an orthotopic model of non-muscle invasive bladder cancer, systemic administration of the anti–PD-L1 checkpoint inhibitor avelumab demonstrated durable antitumor responses and long-term survival mediated by CD4 and CD8 T cells.
[Mechanisms of action of BCG: towards a new individualized therapeutic approach?].
  • F. Saint, J. Patard, D. Chopin
  • Biology, Medicine
    Progres en urologie : journal de l'Association francaise d'urologie et de la Societe francaise d'urologie
  • 2000
The understanding of these mechanisms of action, urinary cytokine assays, a better definition of cytotoxic cells and their role, molecular analysis of the tumour and probably certain genetic characteristics of the host will allow the elaboration of more effective immunization protocols by defining an individualized therapeutic approach.
Immune mechanisms in bacillus Calmette-Guerin immunotherapy for superficial bladder cancer.
The bladder as a confined compartment, in which high local concentrations of the immunotherapy agent and effective recruitment of immune cells can be achieved, serves as an ideal target organ for this type of immunotherapy approach.
BCG-induced interleukin-6 upregulation and BCG internalization in well and poorly differentiated human bladder cancer cell lines.
Upregulation of IL-6 production due to BCG internalization by poorly differentiated bladder carcinoma cells may be part of the mode of action of intravesical BCG therapy.
Mechanisms of action of bacillus Calmette-Guérin in the treatment of superficial bladder cancer
SummaryLocal immunotherapy with bacillus Calmette-Guérin (BCG) is an effective treatment to prevent recurrence and progression of superficial bladder cancer, but the antitumor mechanism of action of
Murine bladder carcinoma cells present antigen to BCG-specific CD4+ T-cells.
The first demonstration of antigen presentation by epithelial tumors supports new approaches to immunotherapy of these malignancies.