Table 1. Summary of studies evaluating the role of cytokines and immunological markers on prediction pf recurrence and progression of non-muscle invasive bladder carcinoma.
| Study | Year | Design | Predictor | Sample | Stage | Intravesical therapy | Results |
|---|---|---|---|---|---|---|---|
| Cytokines | |||||||
| Thalmann et al. (25) | 2000 | Prospective | IL-8, IL-18 | Urine | Ta, T1, CIS | BCG | High level of IL-8 in the first 6 hours after BCG instillation predictor of recurrence-free survival; high level of IL-18 in the first 12 hours after BCG predictor of recurrence-free survival |
| Saint et al. (24) | 2003 | Prospective | IL-2, IL-10 | Urine | Ta, T1, CIS | BCG | IL-2 overproduction predictor of higher recurrence- and progression-free survival |
| Ludwig et al. (30) | 2004 | Prospective | TRAIL | Urine | Ta, T1, CIS | BCG | Predictor of BCG response |
| Shintani et al. (28) | 2007 | Prospective | GM-CSF, TNF-alpha, G-CSF, IL-1beta, IL-8, IFN-gamma, and IL-12 | Urine | Ta, T1, CIS | BCG | High level if TNF-alpha 4 h after the instillation predictor of low recurrence |
| Cai et al. (26) | 2007 | Prospective | IL-6, IL-10 | Urine | Ta, T1, CIS | BCG | IL-6/10 predictor of recurrence |
| Kamat et al. (31) | 2016 | Prospective | IL-6, IL-1ra, IL-2, IL-1b, IL-8, IL-10, IL-12 (p40), IL- 12 (p70), IL-18, IFN-g, TNF-a, and TRAIL | Urine | Ta, T1, CIS | BCG | CyPRIT nomogram score predictor of recurrence |
| Immunological markers | |||||||
| Nunez-Nateras et al. (37) | 2014 | Retrospective | Th1 and Th2 immune response | Tissue | CIS | BCG | Pre-existing Th1 immunologic response within the tumor predictor of BCG-failure |
| Pichler et al. (35) | 2016 | Prospective | Tumor-associated macrophages (TAMs; CD68, CD163); B lymphocytes (CD20); T-lymphocyte subsets (CD3, CD4, CD8, GATA3, T-bet, FOXP3, and CD25) | Tissue | Ta, T1, CIS | BCG | CD4+ and GATA3+ T cells predictors of prolonged recurrence-free survival; TAMs, Tregs, and T-bet+ T cells predictors of shorter recurrence-free survival |
| Pichler et al. (29) | 2017 | Prospective | Th1 (neopterin, tryptophan, kynurenine, kynurenine-to-tryptophan ratio (KTR), IL-12, IFN-g, soluble TNF-R75 and IL-2Ra); Th2 components (IL-4, IL-10) | Blood urine tissue | Ta, T1, CIS | BCG | GATA3/T-bet ratio, neopterin, and KTR predictor of response |
| Chevalier et al. (36) | 2017 | Prospective | T cell to MDSC ratio | Urine | Ta, T1, CIS | BCG | T cell to MDSC ratio <1 predictor of lower recurrence-free survival |
| Wankowicz et al. (33) | 2017 | Prospective | PDL-1 | Tissue | T1 | BCG | No correlation |
| Desgrandchamps et al. (34) | 2018 | Prospective | CD8+ILT2+ T cells | Tissue blood | Ta, T1, CIS | BCG or chemotherapy | CD8+ILT2+ T cells and risk of recurrence |
CIS, carcinoma in situ; BCG, bacillus Calmette-Guérin.