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Bladder cancer ranks tenth in worldwide cancer incidence. With 550,000 newly diagnosed cases in 2018. It is the 7th most common cancer in men and the 17th most common cancer in women.
In Egypt the incidence rate of cancer bladder in (2008-2011) 6.94% both sexes and (10.7%) among men.
Bladder cancer, with the third highest rate of somatic mutations. After lung and melanoma. That expresses high levels of neoantigens and ligands, such as PD-L1, that can inhibit effector T-cell function and T-cell activation.
Checkpoint inhibition targets T cell regulation, increasing T cell and antitumor activity by suppressing inhibitor signals, in addition to the previously known T cell receptor (TCR) activation, there are many co-stimulatory and inhibitory molecules on the surface of T cells and that these influence T cell behaviors. The most important of these are cytotoxic T-lymphocyte associated protein-4 (CTLA-4) and programmed cell death 1 receptor (PD-1) and its ligands (PDL1).
Programmed death ligand-1 (PD-L1) is a T-cell regulatory molecule that may be expressed on the surface of tumor and tumor-infiltrating immune cells. The PD-L1/PD-1 pathway has been shown to be important in cancer progression.
This is a prospective, single arm, cross sectional study which was carried on newly diagnosed 30 patients with epithelial urinary bladder cancer (MIBC and metastatic).
The prognostic and predictive role of TILs in baseline, was examined in pretreatment biopsies of urothelial bladder cancer regarding its significant role and the cutoff point (>=5%) for the actual PD-L1 expression and differentiation between high and low TILs.
Survival analysis was performed using Kaplan- Meier method for disease free survival (DFS) and overall survival (OS); the mean PFS was 9.3 months and the mean OS was 10.633 months. The 1 year PFS was 63.30%, and the 1 year OS is 80.0%.
In our study we confirmed that high PD-L1 expression is correlated with prognosis, as patients with high PD-L1tumor expression cells had lower DFS and OS.
The tumor PD-L1 overexpression had high significant impact on PFS where patients who had PD-L1overexpression had mean 7.2 months compared to 11.4 months in patients who had low tumor PD-L1 expression (P value=0.004). also had significant impact on OS where patients who had high tumor PD-L1 overexpression had mean OS 9.633 months compared to 12.00 months in patients who had low tumor PD-L1 expression, (P value= 0.047).
Indirect relation between tumor PD-L1 tumor overexpression and PFS and OS. (P value=0.000), so the more tumor PD-L1 overexpression the worst prognosis as decreased PFS and OS.
There was no correlation between PD-1 expression level and prognosis. Also there was no correlation with some clinical-pathological variables (age, sex, tumor size, lymph node positive, LVI, histological subtypes and tumor grade).
High PD-L1 expression suggests tumor-associated immune tolerance and escape from immune surveillance, which is one of the hallmarks of cancer cell immune evasion.
The study also supported the hypothesis that positive PD-L1 expression based on staining different cellular populations (tumor cells, tumor-infiltrating ICs, or both) might be associated with improved response to PD-1/PD-L1 inhibitors in UC (urinary bladder cancer) patients.
• We should have standard cutoff point to define high and low TIL level as the heterogeneity in different studies results may be due to lack of uniform definition of PD-L1 positivity and lack of standard assays for PD-L1 expression, with different semi-quantitative scores of the PD-L1 expression status in clinical trials and different PD-L1 antibody clones.
• Tumor infiltrating lymophocytes help in identification of patients with different prognosis during and after treatment.
• The assessment of tumor-associated PD-L1 in Specimens may provide a rationale for intensive treatment of high-risk cases.
• The manipulation of tumor-associated PD-L1 or PD-1 signaling in TILs may provide an improved outcome in the treatment of urothelial cancer.
Advantages and Limitations
The assessment of tumor-associated PD-L1 in Specimens may help in identification of patient’s prognosis; provide a rationale for intensive treatment of high-risk cases and promising therapeutic target for bladder cancer.
The study has some limitations such as the relatively small patient’s number related to the case selection focused only on muscle invasive and metastatic urotheloial bladder cancer patients and short duration of follow up.