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Cancer immunology, immunotherapy : CII

Intratumoral Th2 predisposition combines with an increased Th1 functional phenotype in clinical response to intravesical BCG in bladder cancer.


PMID 28005163

Abstract

Th1-type immunity is considered to be required for efficient response to BCG in bladder cancer, although Th2 predisposition of BCG responders has recently been reported. The aim was to evaluate the relationship of Th1 and Th2 components in 23 patients undergoing BCG treatment. Peripheral blood, serum and urine samples were prospectively collected at baseline, during and after BCG. Th1 (neopterin, tryptophan, kynurenine, kynurenine-to-tryptophan ratio (KTR), IL-12, IFN-γ, soluble TNF-R75 and IL-2Rα) and Th2 (IL-4, IL-10) biomarkers as well as CD4 expression in T helper (Th), effector and regulatory T cells were determined. Local immune cell subsets were measured on formalin-fixed, paraffin-embedded cancer tissue by immunohistochemistry to examine expression of transcription factors that control Th1 (T-bet) and Th2-type (GATA3) immunity. We confirmed a Th2 predisposition with a mean GATA3/T-bet ratio of 5.51. BCG responders showed significantly higher levels of urinary (pxa0=xa00.003) and serum neopterin (pxa0=xa00.012), kynurenine (pxa0=xa00.015), KTR (pxa0=xa00.005), IFN-γ (pxa0=xa00.005) and IL-12 (pxa0=xa00.003) during therapy, whereas levels of IL-10 decreased significantly (pxa0

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61250
DL-Kynurenine, ≥95.0% (NT)
C10H12N2O3