A soluble lymphocyte activation gene-3 (sLAG-3) protein as a prognostic factor in human breast cancer expressing estrogen or progesterone receptors

In contrast to the long-held belief that breast cancer is a weakly immunogenic tumor, accumulating evidence indicates an immune infiltrate is an invariable finding in breast cancers, raising hopes that immunotherapy for breast cancers may succeed in targeted patients, specifically those with either regional or minimal residual disease. However, no immunologically related prognostic factor has yet been established that may help to define subsets of patients who are more prone to respond to immunotherapy. High levels of soluble LAG-3 protein (sLAG-3) in sera has previously been shown to be associated, as a Th1 marker, to resistance to tuberculosis in large series of patients. We therefore hypothesized that, if cell-mediated immune mechanisms are indeed important for improved prognosis, high levels of sLAG-3 might be correlated with improved survival in some subsets of breast cancer patients. Studying a cohort of 246 patient's sera collected in 1994 at time of first diagnosis, we found that both disease-free and overall survival rates were greater in patients with estrogen or progesterone receptor positive tumor cells who had detectable levels of sLAG-3 at diagnosis versus patients with undetectable sLAG-3 levels. These results indicate that sLAG-3 may be a valuable marker for prognosis in some subsets of breast cancers and, more importantly, that cell-mediated mechanisms such as Th1 responses do have an impact on survival, a pre-requisite before the setting-up of immunotherapy protocols as a form of adjuvant therapy for breast cancer.