2011
DOI: 10.1016/j.immuni.2010.12.011
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CD169-Positive Macrophages Dominate Antitumor Immunity by Crosspresenting Dead Cell-Associated Antigens

Abstract: The generation of tumor-directed cytotoxic T lymphocytes is considered crucial for the induction of antitumor immunity. To activate these CD8(+) T cells, antigen-presenting cells (APCs) must initially acquire tumor cell-associated antigens. The major source of tumor antigens is dead tumor cells, but little is known about how APCs in draining lymph nodes acquire and crosspresent these antigens. Here we show that CD169(+) macrophages phagocytose dead tumor cells transported via lymphatic flow and subsequently cr… Show more

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Cited by 390 publications
(425 citation statements)
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“…Recently Tanaka and colleagues demonstrated that CD169 + macrophages can cross-present apoptotic tumor antigens in draining lymph nodes to elicit protection from tumor establishment in a model of melanoma (33). This finding is seemingly at odds with both our present report as well as the Tanaka group's previous data, indicating that CD169 + macrophages are critical for apoptotic cell-antigen tolerance in the spleen (8).…”
Section: Discussioncontrasting
confidence: 84%
See 1 more Smart Citation
“…Recently Tanaka and colleagues demonstrated that CD169 + macrophages can cross-present apoptotic tumor antigens in draining lymph nodes to elicit protection from tumor establishment in a model of melanoma (33). This finding is seemingly at odds with both our present report as well as the Tanaka group's previous data, indicating that CD169 + macrophages are critical for apoptotic cell-antigen tolerance in the spleen (8).…”
Section: Discussioncontrasting
confidence: 84%
“…However, there are significant differences in basal environmental exposure that would be expected to alter macrophage function. Moreover, in the tumor-model system the apoptotic cells were delivered subcutaneously and were allowed to apoptose for 24 h before injection (33). Thus, the anatomical differences, coupled with the later stages of apoptosis and alternate route of administration, likely account for the differences in immune response we observed.…”
Section: Discussionmentioning
confidence: 95%
“…5B). Although we cannot entirely exclude a residual cross-presentation capacity of other DC (34) or macrophage subsets (35) in the Batf3 null mice, this contribution to Ag presentation has been reported to be inefficient in this setting (17,36). When taken together with the OT-1 CD8 + T cell priming observed by our adoptive DC transfer system in the K bm1 mouse (Fig.…”
Section: Discussionmentioning
confidence: 82%
“…Studies in murine systems have shown that CD169 C Mf contribute to antigen retention and cross-presentation of antigens to CD8 C T cells in the LN, thereby functioning as powerful APCs that significantly contribute to CTL responses. 21,23,26 The mechanism of generating CD169 C CD8 C T cells is presently unknown. T lymphocytes located adjacent to CD169 C Mf have been shown to be stained for CD169 due to blebs from CD169 C Mf undergoing fragmentation.…”
Section: Discussionmentioning
confidence: 99%
“…20 In mouse LNs, anti-CD169 antibodies label subcapsular sinus and medullary macrophages (Mf), and these CD169 C Mf are poised to rapidly encounter pathogens, antigens, and exosomes that reach the LN. [21][22][23][24][25] A recent study demonstrated that CD169 C Mf could effectively generate CTL responses by cross-priming CD8 C T cells, which in turn, conferred immunity against re-exposure to the malignant cells. 26 The expression of CD169 in tumor-draining LN and its association with survival in CRC patients has been recently reported 27 ; however, the specific composition and function of CD169 C cells in tumor-draining LNs of cancer patients remain largely unknown.…”
Section: Introductionmentioning
confidence: 99%