Immunomodulation May Be New Useful Approach to Treat Lung Cancer

A new finding suggests that inhibiting the cytokine interleukin-17A (IL-17A), produced by inflammatory cells of the immune system, may be a novel approach in the treatment of lung tumors. Researchers from the Institute of Molecular Pneumology in Germany have shown that blocking this specific cytokine improves survival in a mouse lung cancer model (DOI: 10.1038/ncomms1609).

CT scan showing a Pancoast's tumor (labeled as P, non–small-cell lung carcinoma, right lung), from a 47-year-old female smoker. Source: User Jmarchn, Wikimedia Commons

Susetta Finotto and colleagues have found that non–small-cell lung cancer (NSCLC) samples have higher levels of IL-17A, a cytokine that is normally produced by T cells that infiltrate the tumor and aid in its vascularization. Previous studies have shown that both ovarian carcinomas and cutaneous T-cell lymphomas secrete IL-17A and that high IL-17A expression correlates with increased vascularization of these tumor types.

The authors of the paper, published this week in Nature Communications, investigated IL-17A levels in NSCLC as this tumor type is known to produce many angiogenic factors including CXCL8/IL-8 which is induced by IL-17A production. IL-8 has been shown to be a crucial factor in the pathogenesis of NSCLC.

In a mouse lung carcinoma model, the authors show that an antibody against IL-17A is able to suppress local lung tumor growth and is able to alter the balance of T cells in the tumor as well as expression of other cytokines. The mouse model used also uncovered a role for T-bet in the regulation of both IL-23 and IL-17A levels in the lung. From observations in both human lung tumor samples and the lung carcinoma mouse model the authors suggest that the tumor environment creates an environment in which IL-23 is prevalent, allowing for increased IL-17A levels and more infiltrating T cells.

Immunotherapy as treatment for cancer has become a very promising field with the recent approval of ipilimumab, an antibody that facilitates the immune system’s natural defense mechanisms against tumors. Many novel immunotherapy agents are attempting to boost the immune system’s attack on tumor cells and to reverse the immunosuppressive properties of the tumor environment by stimulating a host immune response.

The current finding shows that IL-17A antibody therapy may be a viable and promising way to treat lung cancer partly by hindering tumor-infiltrating T regulatory cells.