P79
Remodelling the bladder immune microenvironment by mycobacterial species with changes in their cell envelope composition
S Guallar-Garrido(2,5) J Senserrich(1) E Gomez-Mora(1) V Urrea(1) B Clotet(1,3,4) T Soldati(5) C Cabrera(1) E Julián(2)
1:AIDS Research Institute IrsiCaixa, Institut de Recerca en Ciències de la Salut Germans Trias i Pujol (IGTP), Spain; 2:Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Spain; 3:Infectious Diseases Department, Hospital Germans Trias i Pujol, Spain; 4:Universitat de Vic Central de Catalunya, Spain; 5:Départment de Biochimie, Faculté des Sciences, Université de Genève, Genève, Switzerland
Bacillus Calmette–Guérin (BCG) is the most effective intravesical treatment for non-muscle-invasive bladder cancer. Nevertheless, it is not always effective and frequently has undesirable side effects. Here we evaluated the bladder immune microenvironment composition and its association with survival after intravesical treatment with a panel of mycobacteria with variation in their cell envelope composition in an orthotopic murine model of bladder cancer. We provide evidence that the induced global immune microenvironment was strikingly different between the two mycobacterial species tested (BCG and Mycobacterium brumae). Compared with M. brumae, BCG triggered a more robust infiltration, with higher frequencies of neutrophils/gMDSCs and inflammatory monocytes, and higher TEM/CD4+ Treg ratios. Conversely, M. brumae treatment triggered higher proportions of activated effector immune cells and reparative monocytes and lower ratios of TEM cells/CD4+ Treg. Notably, the mycobacterial cell envelope composition in M. brumae had a strong impact on the tumour immune microenvironment, shaping the B-cell composition, T-cell maturation profile and myeloid compartment, thus improving the inflammatory and regulatory/suppressive balance and survival. Overall, we demonstrate that mycobacterial intravesical treatment modulates the bladder tissue immune microenvironment. The induced immune infiltration is species-specific, shaped by mycobacterial cell envelope composition. Therefore, the global bladder tumour immune microenvironment can be remodelled, improving the quality of infiltrating immune cells, the balance between inflammatory and regulatory/suppressive responses and increasing survival.