Trillium Therapeutics Inc (TRIL)

[DFRAI]

CD47-blocking immunotherapies stimulate macrophage-mediated destruction of small-cell lung cancer

http://www.jci.org/articles/view/81603

Emerging studies indicate that both the innate and adaptive immune systems may contribute to the efficacy of CD47-blocking therapies. The CD47/SIRPa axis may be an early checkpoint in immune activation, regulating phagocytosis and antigen uptake to then promote antigen presentation to T cells. Both macrophages and dendritic cells may mediate this link in response to CD47 blockade (39, 40). Furthermore, a recent study demonstrated that CD47-blocking therapies may enhance the efficacy of other immune checkpoint inhibitors, such as agents targeting the PD-1/PD-L1 axis (47). We found that Cd47 ablation was effective at inhibiting tumor growth in both immunocompromised and immunocompetent models, where immunosuppressive cells such as Treg could limit antitumor responses (48). SCLC exhibits a high mutation burden (49), likely due to its association with heavy tobacco use and frequent inactivation of p53 and pRB (50); therefore, it may be particularly responsive to therapies that engage the adaptive immune system. Therapies targeting T cell immune checkpoints are now being tested in SCLC (51, 52) and may cooperate with CD47-blocking approaches (40, 47).