Siglec-1⁺ macrophages in anti-tumor immunity

Macrophages expressing the sialic acid-binding lectin Siglec-1 are positioned strategically for uptake and filtering of antigenic material circulating through the lymphatic system into the subcapsular sinus of lymph nodes and through the blood into the marginal zone of the spleen. Siglec-1⁺ macrophages are also found in many tissues, frequently displaying an inflammatory profile. In secondary lymphoid organs, these cells are strategically positioned and play a role in adaptive immune responses by B, NK and T lymphocytes. A potential role of the cells in antitumor immunity has attracted significant scientific interest. This concept is supported by a report of dendritic cell-independent priming of a protective antitumor response by lymph node Siglec-1+ macrophages. Indeed, examination of preclinical models and human tumors has provided evidence for a dominant protective effect of lymph node Siglec-1+ macrophages in major types of solid tumors e.g. breast or colorectal cancer. In contrast, Siglec-1+ macrophages within tumor tissue have been found to be associated variably with favorable or unfavorable outcome depending on the model and tumor studied. We have recently demonstrated in mouse models that splenic Siglec-1+ macrophages in themarginal zone can prime protective tumor immunity against both tumors disseminating through the blood and tumors invading the spleen in the absence of type 1 conventional dendritic cells. Considering this, we postulate Siglec-1+ macrophages in all secondary lymphoid organs can prime potent antitumor responses. We propose that this capacity could be exploited for therapeutic stimulation of tumor immunity.