Lung cancer is the leading cause of cancer death in men and women, both in the United States and the world. The current 5-year survival rate for lung cancer in the United States for all races is a discouraging 16% and has not changed dramatically during the past 30 years. The biggest reason for the discouraging survival statistics is that the majority of lung cancer subjects present with late-stage disease that is not curable by current therapies i.e. chemotherapy and radiation. However, in the last several years novel therapies have emerged to make lung cancer therapy better tolerated and more effective. As tumor immunologists, we are particularly interested in developing an immunotherapy that will help to engage the immune system in targeting and destroying tumor cells. In a comprehensive survey of the immune infiltrate in non-small cell lung cancer (NSCLC) patients, we discovered that the frequency of the B cell infiltrate in the tumor versus the normal tumor-adjacent tissue was significantly increased in comparison to other immune subsets, specifically, CD4, CD8, and regulatory T cells as well as NK and NKT cells. Further preliminary studies on the characterization of these B cells suggest that they have proliferated and acquired a memory phenotype. We will continue to characterize the B cells in the tumor microenvironment to determine if they are activated as well as functional. If the B cells in the tumor microenvironment are activated, we will test if the cells are responsive to antigens currently in clinical trial like MUC-1 as well as new antigens in the cancer-testis classification like XAGE-1b. We will test if the antigens are stimulating the B cells through the BCR and if these antigens will be presented to CD4 T cells in vitro, which would lead to the stimulation of the CD4 T cells. If the B cells are not activated, we will then query whether or not the B cells could have a suppressive phenotype, which will be determined by assaying the types of cytokines produced by the B cells using a cytokine array. As we continue to further characterize the B cells, we will also continue to monitor the various immune subsets in the three subtypes of NSCLC: adenocarcinoma, squamous cell carcinoma and large cell carcinoma. This immunophenotyping of the immune subsets will aid us in the identification of the appropriate immune cell populations to target for immunotherapy in the three subtypes of NSCLC. Ultimately, we aim to identify a novel target for an immunotherapy clinical trial in lung cancer patients.

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©2013 American Association for Cancer Research.
2013