JAK2 Expression is Associated with Tumor-Infiltrating Lymphocytes and Improved Breast Cancer Outcomes: Implications for Evaluating JAK2 Inhibitors
A partir de données issues de plusieurs cohortes de patientes atteintes d'un cancer du sein, cette étude met en évidence le rôle joué par une surexpression de JAK2 dans la réduction du risque de récidive, puis évalue les implications de ces résultats pour les essais cliniques d'inhibiteurs de JAK2
Janus kinase-2 (JAK2) supports breast cancer growth and clinical trials testing inhibitors are underway. JAK2 is also expressed beyond the tumor epithelium, including in immune cells, and whether JAK2 mRNA levels in breast tumors correlate with outcomes has not been evaluated. Using a case-control design, JAK2 mRNA was measured in 223 archival breast tumors and associations with distant recurrence were evaluated by logistic regression. The frequency of correct pairwise comparisons of patient rankings based on JAK2 levels versus survival outcomes, the concordance index (CI), was evaluated using data from 2,460 patients in 3 cohorts. In the case-control study, increased JAK2 was associated with a decreasing risk of recurrence (multivariate p=0.003, n=223). Similarly, JAK2 was associated with a protective CI (<0.5) in the public cohorts: NETHERLANDS CI=0.376, n=295; METABRIC CI=0.462, n=1,981; OSLOVAL CI=0.452, n=184. Furthermore, JAK2 strongly correlated with the favorable prognosis LYM metagene signature for infiltrating T cells (r=0.5, p<2x10-16, n=1,981) and with severe lymphocyte infiltration (p=0.00003, n=156). Moreover, the JAK1/2 inhibitor ruxolitinib potently inhibited the anti-CD3-dependent production of interferon-γ, a marker of the differentiation of T-helper cells along the tumor-inhibitory Th1 pathway. The potential for JAK2 inhibitors to interfere with the anti-tumor capacities of T cells should be evaluated.