Although mechanistic experiments in murine models are essential to dissect the pathways by which B cells and humoral immunity contribute to lung cancer pathogenesis, it is important to keep in mind that immunological responses in murine models may not be transferable to humans due to intrinsic differences between species. For instance, whereas several studies have demonstrated that IL-7 activation of STAT5 is essential for the development of mouse B-cells and that disruption of this signaling axis results in the arrest of B-cell maturation at the pro-B stage (3), in humans, the regulatory role and timing of IL-7/IL-7Rα/STAT5 signaling during B-cell development remains a largely controversial topic. The classical model of human lymphopoiesis established that IL-7 is required for the proliferation of T-cell progenitors but not for the proliferation of B-cell progenitors. More recently, however, it has been reported that in humans, continuous pSTAT5 response to IL-7 is restricted to a rare population of B cell precursors, in which STAT5 phosphorylation can also be induced by TSLP (4). Furthermore, it has been shown that human B-cell production is increasingly dependent on IL-7Rα signalling which can be provided by IL-7 or TSLP (5). Together, these studies demonstrate that human B lymphopoiesis is affected by IL-7/IL-7Rα signaling, although perhaps to a lesser extent than in mice. This opens up the possibility that IL-7 may indeed affect anti-tumor immunity in humans by modulating not only T-cell but also B-cell responses.

However, there are conflicting reports regarding the effect of IL-7 on tumor growth. Whereas some studies have found that IL-7 can restore the number and function of CD8+ and CD4+ T-cells, others have found that it induces the expression of PD-1 and its ligands (6) and that IL-7Rα expression is associated with the immunosuppressive capacity of Tregs.