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.
- Received October 23, 2013.
- Revision received December 17, 2013.
- Accepted January 2, 2014.
- Copyright © 2014, American Association for Cancer Research.