Nicotine affects anti-tumor immunity elicited by therapeutic vaccine

Objectives: Smokers constitute a majority of patients with cancer and hence, are frequently subjected to vaccine therapy. Dendritic cells (DCs) are specialized cells that tailor host response against cancer by inducing the development of Th1 cells, which promote the function of tumor-specific effector cells. We recently reported that nicotine, an immunomodulatory component of cigarette smoke, weakens host response by affecting the development of Th1 cells through impairment of the DC system. Our data raised doubts on the ability of cancer vaccines to generate sufficient DC-primed immune responses in smokers receiving therapy. We therefore, investigated the effectiveness of therapeutic cancer vaccine in tumor-bearing mice exposed to nicotine.

Methods: Wild-type C57BL/6J mice were exposed to saline (control) or nicotine (2mg/kg/day) using osmotic pumps. These mice were then inoculated on day 0 with 1x10⁶ ovalbumin (OVA)-expressing EG7 tumor cells. On days 4 and 10, tumor-bearing mice were vaccinated subcutaneously with OVA protein (2mg) and adjuvant lipopolysacharride (LPS, 50μg). The mice were palpated for the regression of the tumor. 21 days after the last vaccination, mice were sacrificed and lymphoid cells were isolated and restimulated in vitro. The ability of tumor-specific effector cells to secrete IFN-γ and to kill the tumor cells was evaluated by ELISA and calcein AM-based cytotoxic assay, respectively.

Results: We found that the vaccine effectively controls the tumor growth in control mice. However, the same vaccine provides little therapeutic tumor regression in nicotine-exposed mice as evidenced by a larger tumor mass. When compared to control mice, lymphoid cells isolated from nicotine-exposed mice produce up to 50% less IFN-γ after re-exposure to tumor antigen and exhibit markedly reduced CTL killing activity against inoculated tumor cells.

Conclusion: Collectively, our data suggests that therapeutic vaccines provide only partial protection in nicotine-exposed individuals. Philip Morris USA Inc., and Philip Morris International.