2026-04-29T16:56:14Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/185362024-11-29T14:50:31Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Masson-Lecomte, Alexandra
author
Maillé, Pascale
author
Pineda, Silvia
author
Soyeux, Pascale
author
Sagrera, Ana
author
Rava, Marta
author
de Maturana, Evangelina Lopez
author
Márquez, Mirari
author
Tardón, Adonina
author
Carrato, Alfredo
author
Kogevinas, Manolis
author
de la Taille, Alexandre
author
Hartmann, Arndt
author
Malats, Nuria
author
Real Arribas, Francisco
author
Allory, Yves
funder
Instituto de Salud Carlos III
funder
Asociación Española Contra el Cáncer
funder
NIH - National Cancer Institute (NCI) (Estados Unidos)
funder
European Association of Urology
2024-02-20T13:24:08Z
2024-02-20T13:24:08Z
2019-08-16
Bladder Cancer . 2019;5(2):159-169
10.3233/blc-180206
2352-3727
Bladder cancer (Amsterdam, Netherlands)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9503287/
36157135
http://hdl.handle.net/20.500.12105/18536
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+ /mm2 were 25/mm2 and 129/mm2 in tumor and stroma respectively in Ta and 111/mm2 and 344/mm2 in T1; p-value = 0.006). CD8+ infiltration in tumor compartment was significantly associated with low FGFR3 expression. CD8+/mm2 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.
eng
CD8+ Cytotoxic Immune Infiltrate in Non-Muscle Invasive Bladder Cancer: A Standardized Methodology to Study Association with Clinico-Pathological Features and Prognosis.
journal article
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