Background: Immunotherapy in bladder cancer seems to give promising results. The purpose of this study is to evaluate the involvement of immune response during bladder carcinogenesis and to compare expression levels in non-muscle invasive bladder cancer (NMIBC) versus muscle-invasive bladder cancer (MIBC). Methods: Expression levels of 3 genes involved in PD1 pathway (PD1, PDL1 and PDL2), 4 genes involved in CTLA4 pathway (CTLA4, CD28, CD80 and CD86) and 27 other immune genes (including LAG3 and TIM3) were assessed by quantitative real time RT-PCR and by immunochemistry in normal and tumoral human bladder samples. Tumors were obtained from 155 patients (25 women and 130 men, mean age 68 years). All patients have signed an informed consent. Pathological tumor staging showed: 71 NMIBC (29 low grade pTa, 14 high grade pTa and 28 high grade pT1), and 84 MIBC (≥ pT2) all of high grade. Results were coupled to a survival analysis. Results:PD1 and PDL1 were significantly overexpressed in MIBC compared to normal bladder tissue (59.5 vs 6.7% and 60.7 vs 0% respectively, p < 0.01), whereas the proportion of overexpression was low in NMIBC (22.5% and 4.2% respectively). Similarly, CTLA4 and one of its ligands CD80 were significantly overexpressed in MIBC as compared to normal bladder tissue (84.5 vs 20.0% and 92.9 vs 6.7% respectively, p < 0.01), whereas CD80 was individually overexpressed in 46.5% of NMIBC without overexpression of CTLA4. There was a high concordance rate between expression levels of the two pathways, according to Spearman test (0.88, p < 0.0001). The results of the molecular analysis were confirmed by immunohistochemistry with a good correlation. There was no correlation between mRNA expression levels of the studied genes and prognosis in terms of relapse / progression for NMIBC and in terms of recurrence-free and overall survival for MIBC. Conclusions: Our results confirm the role of immune checkpoints in bladder carcinogenesis, with a good correlation between RT-PCR and immunochemistry analysis, and opening new therapeutic perspectives, especially for invasive tumors. However, these deregulations do not concern NMIBC and seem not to be associated with survival outcomes.