Differential impairment of regulatory T cells rather than effector T cells by paclitaxel-based chemotherapy.

Characterized as a mitotic inhibitor, paclitaxel has gained importance as a promising agent for the treatment of advanced non-small cell lung cancer (NSCLC). However, whether paclitaxel has immune modulatory effects remains unclear. In this study, we analyzed 55 peripheral blood samples from NSCLC patients who underwent paclitaxel-based chemotherapy. We found that among the lymphocyte subsets, paclitaxel selectively decreased the size of the regulatory T cell (Treg) population rather than other subsets including effector T cells (Teff). Apoptosis by upregulating the expression of the cell death receptor Fas (CD95) contributed to the reduced cell number of Treg. Importantly, the inhibitory function of Treg was significantly impaired, while the production of Th1 cytokines IFN-gamma and IL-2 and the expression of the activation marker CD44 among CD4(+) and CD8(+) T cells were augmented after paclitaxel treatment. These results strongly demonstrated that paclitaxel-based chemotherapy played important roles in modulating immune responses.

Does chemotherapy augment anti-tumor immunotherapy by preferential impairment of regulatory T cells?

Chemotherapy, the treatment modality of choice for advanced cancers, is considered immunosuppressive due to its depletion of immune cells. Hence, chemotherapy is traditionally thought to adversely affect anti-tumor immune responses and antagonistic to tumor immunotherapy. Contrary to conventional belief, recent studies have shown that combining chemotherapy with immunotherapy resulted in enhanced anti-tumor immunity and improved therapeutic outcome. The mechanisms by which the use of chemotherapy paradoxically benefits immunotherapy await elucidation. CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg) are a lymphocyte subset which plays a crucial role in inhibiting tumor-reactive effector cell functions and suppressing anti-tumor immunity. We hypothesize that chemotherapy benefits immunotherapy by preferentially impairing Treg, in effect eliminating immunosuppressive elements and augmenting the immune function of anti-tumor effector cells. Clarification of how chemotherapy exerts its immunomodulatory effects will aid in the development of better combination strategies of chemoimmunotherapy in the treatment of cancer.