Clinical significance of CD73 in triple-negative breast cancer : multiplex analysis of a phase III clinical trial
Menée à partir de l'analyse par immunofluorescence et imagerie de 122 échantillons tumoraux fixés au formaldéhyde et inclus en paraffine après prélèvement sur des patientes atteintes d'un cancer du sein triplement négatif et participant à un essai de phase III évaluant un traitement adjuvant, cette étude évalue l'association entre le niveau d'expression de la protéine CD73 et le pronostic
Background : CD73 is an ecto-enzyme that promotes tumor immune escape through the production of immunosuppressive extracellular adenosine in the tumor microenvironment. Several CD73 inhibitors and adenosine receptor antagonists are being evaluated in phase I clinical trials.
Patients and methods : Full-face sections from formalin-fixed paraffin-embedded primary breast tumors from 122 samples of triple-negative breast cancer from the BIG 02-98 adjuvant phase III clinical trial were included in our analysis. Using multiplex immunofluorescence and image analysis, we assessed CD73 protein expression on tumor cells, tumor-infiltrating leukocytes and stromal cells. We investigated the associations between CD73 protein expression with disease-free survival, overall survival and the extent of tumor immune infiltration.
Results : Our results demonstrated that high levels of CD73 expression on epithelial tumor cells were significantly associated with reduced disease-free survival, overall survival and negatively correlated with tumor immune infiltration (Spearman’s R= -0.50, p < 0.0001). Patients with high levels of CD73 and low levels of tumor-infiltrating leukocytes had the worse clinical outcome.
Conclusions : Taken together, our study provides further support that CD73 expression is associated with a poor prognosis and reduced anti-tumor immunity in human triple-negative breast cancer and that targeting CD73 could be a promising strategy to reprogram the tumor microenvironment in this breast cancer subtype.
Annals of Oncology , résumé, 2016