Chemokines play an important role in the generation of the immune system and in virtually every aspect of an immune response. The role of chemokines in antitumor immunity has been less straightforward to discern. A dichotomy exists in the field. One area of research has focused on the impact of tumor-derived chemokines, implicating them in everything from metastases to immune suppression. Another area of research has been dedicated to the introduction of chemokines into tumor cells in order to facilitate immune cell recruitment. In this review these two areas of investigation will be explored.

Monocyte chemoattractant protein-1 (MCP-1, CCL2) is produced by many different types of cells. In the current investigation, the effect of tumor-derived CCL2 on macrophages was evaluated to determine the extent to which this chemokine influenced the innate immune response to cancer. To do this, we used the 4T1 murine mammary carcinoma cell line that constitutively expresses CCL2 and generated 4T1 expressing an antisense CCL2 transcript. The antisense-CCL2-expressing 4T1 produced no detectable CCL2. Macrophages from female BALB/c mice were exposed to supernatants from these tumor cells. The results showed that tumor-derived CCL2 was capable of modulating cytokine gene expression but not protein production in resting, activated, and tumor-associated macrophages. In addition, tumor-derived CCL2 did not affect phagocytic activity, nitric oxide production, or cytolytic activity of the macrophages. Overall, these data suggest that tumor-derived CCL2 does not directly influence macrophage-mediated antitumor activity.

To determine the extent to which splenic T cells were affected by Schistosoma mansoni infection, we investigated the ability of the T cells to produce interferon (IFN)-gamma, as well as their chemotactic ability 7 wk PI. In this study, we report that splenic T cells from Balb/c mice with S. mansoni infections were capable of producing levels of IFN-gamma comparable with splenic T cells from naive mice. However, the T cells exhibited altered chemotactic activity, as evidenced by an inability to respond to secondary lymphoid-tissue chemokine (SLC/CCL21). Although no difference in chemokine expression was found between the spleens of infected versus control mice, chemokine production was greater in the livers of infected versus control mice. Collectively, these data indicate that Balb/c mice with 7-wk S. mansoni infection possess splenic T cells with altered chemotactic activity and that the alterations may be a consequence of the granulomatous response in the liver.

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