AI Article Synopsis

  • The study focuses on analyzing CD8+ cytotoxic lymphocytes in bladder cancer, particularly in non-muscle invasive bladder cancer (NMIBC), to understand their role in the immune response against tumors.
  • A standardized method was developed for estimating CD8+ cell counts using tissue samples from a large cohort, revealing significant spatial heterogeneity in immune cell infiltration between different tumor stages.
  • The findings indicate that CD8+ infiltration varies with tumor stage but does not correlate with patient prognosis, highlighting the need for careful study design in future research.

Article Abstract

Background: Major interest lies in the evaluation of immune infiltrate in bladder cancer. CD8+ cytotoxic lymphocytes are key effectors of adaptive immune response.

Objectives: The aims of the study were to set up a standardized methodology for CD8+ lymphocytes estimation in NMIBC and investigate how intra-tumoral heterogeneity influences CD8+ immune infiltrate.

Methods: We considered 995 NMIBC included in the Spanish Bladder Cancer (SBC)/EPICURO Study. Duplicate 0.6mm TMA spots and paired full sections (FS) for 50 selected cases were double stained with anti-pan cytokeratin antibody and anti-CD8 antibody. Slides were digitalized and CD8+ cells were automatically counted after tissue recognition (tumor vs stroma). Spatial heterogeneity was assessed and a resampling strategy was applied to estimate the proper number of 0.6mm TMA spots providing an adequate CD8+ cell estimate. Association between CD8+ count and expression of urothelial differentiation markers was estimated. Cox regression models were performed to assess association between CD8+ cell count and risk of recurrence and progression.

Results: Microscopic examination of full sections showed spatial heterogeneity for CD8+ infiltrates. Simulation analyses demonstrated that 5 TMA regions provided a correct sampling of tumor and stromal compartments in Ta while 2 and 6 TMA regions were necessary in T1, respectively. CD8+ cells infiltration was associated with stage, regardless of the histological compartment analyzed (median CD8+ /mm were 25/mm and 129/mm in tumor and stroma respectively in Ta and 111/mm and 344/mm in T1; -value = 0.006). CD8+ infiltration in tumor compartment was significantly associated with low FGFR3 expression. CD8+/mm count in the tumor compartment was not associated with prognosis.

Conclusion: Differences identified between Ta and T1 tumours supported the hypothesis that rigorous efforts should be placed in proper study design. These results provide a new framework to investigate microenvironment complexity in bladder cancer.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9503287PMC
http://dx.doi.org/10.3233/blc-180206DOI Listing

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