Immune alterations and emerging immunotherapeutic approaches in lung cancer

Subjects with lung cancer were shown to present a variety of immune abnormalities including cellular immune dysfunction, cytokine alterations, and antigen presentation defects. As discouraging results are commonly seen with the existing therapies in lung cancer, more innovative treatment strategies are needed.

The authors review comprehensively the immune abnormalities in individuals with lung cancer, describe the lung cancer immunotherapy candidates that are most advanced in their clinical development, and summarize recent data from clinical trials of these agents.

Enhancing the immune system represents an appealing avenue for lung cancer therapy. Several immunomodulating agents have activity in this regard including ipilimumab, a monoclonal antibody against the CTLA-4, and talactoferrin, a dendritic cell activator. In addition, a significant activity was shown with belagenpumatucel-L, a whole-cell-based vaccine that blocks the action of TGF-β2. Other promising vaccines are protein-specific vaccines against tumor antigens such as MAGE-A3, EGF, and MUC1. Although some of these immunotherapies may have lackluster performance as single agents in advanced disease, more impressive results are seen in combination with chemotherapy agents. Given their proven activity in lung cancer, these immunotherapies may soon become a powerful addition to the oncologist's toolbox.