The CD169 sialoadhesin molecule mediates cytotoxic T‐cell responses to tumour apoptotic vesicles

Black, Lane Vincent Charles; Saunderson, Sarah C.; Coutinho, Frazer; Muhsin-Sharafaldine, Morad-Rémy; Damani, Tanvi; Dunn, Amy C.; McLellan, Alexander D.

doi:10.1038/icb.2015.111

Cited by 30 publications

(58 citation statements)

References 36 publications

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“…After injection of apoptotic vesicles derived from antigen‐pulsed tumor cells, the mouse immune system is capable of mounting an enhanced cytotoxic response to antigen‐pulsed target cells. This response is further enhanced in CD169 −/− mice suggesting a role for CD169 in the capture of apoptotic vesicles and attenuation of the cytotoxic immune response …”

Section: Siglecs and The Capture Of Tumor‐derived Vesiclesmentioning

confidence: 98%

“…In addition to exosomes, apoptotic vesicles derived from primary B cells, EL4 lymphoma cells, and B16 melanoma cells all express α2,3‐linked sialic acids . EL4 lymphoma‐derived apoptotic vesicles as well as B cell and B16 melanoma derived apoptotic vesicles prominently co‐localized with CD169 in murine spleen sections in vitro, and EL4‐derived apoptotic vesicles co‐localized with CD169 + macrophages to a greater extent than outer marginal zone and red pulp macrophages in vivo.…”

Section: Siglecs and The Capture Of Tumor‐derived Vesiclesmentioning

confidence: 99%

“…82 EL4 lymphoma-derived apoptotic vesicles as well as B cell and B16 melanoma derived apoptotic vesicles prominently co-localized with CD169 in murine spleen sections in vitro, and EL4derived apoptotic vesicles co-localized with CD169 + macrophages to a greater extent than outer marginal zone and red pulp macrophages in vivo. Furthermore, spleen sections from CD169 deficient mice did not exhibit any interaction with EL4 apoptotic vesicles 82. Apoptotic vesicles provide a debris clearance mechanism while also providing an important source of foreign and self-antigens, including tumor antigens.…”

mentioning

confidence: 96%

“…Apoptotic vesicles provide a debris clearance mechanism while also providing an important source of foreign and self-antigens, including tumor antigens. After injection of apoptotic vesicles derived from antigenpulsed tumor cells, the mouse immune system is capable of mounting an enhanced cytotoxic response to antigen-pulsed target cells.This response is further enhanced in CD169 −/− mice suggesting a role for CD169 in the capture of apoptotic vesicles and attenuation of the cytotoxic immune response 82. Recently, in vivo mouse experiments have provided evidence for the importance of CD169 + macrophages in the subcapsular sinus of tumor-draining lymph nodes in preventing the spread of melanoma tumor-derived EVs deeper into the lymph node and limiting | 185 FRASCHILLA And PILLAI the development of vesicle-B cell interactions that lead to tumorpromoting autoantibody production 83.…”

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confidence: 99%

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Viewing Siglecs through the lens of tumor immunology

Fraschilla

Pillai

2017

Immunological Reviews

106

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Summary Many Siglecs function as inhibitory receptors on innate and adaptive immune cells and may contribute to the attenuation of immune responses to tumors. Siglec 9 on neutrophils and Siglec 7 on NK cells are prominent examples of inhibitory Siglecs that can potentially dampen anti-tumor immunity. CD169 is a Siglec that may function as an adhesion molecule and a facilitator of the recognition and internalization of sialic acid decorated apoptotic bodies and exosomes derived from tumors. It can potentially contribute to both the attenuation as well as the facilitation of anti-tumor immunity. Siglecs have been best studied in the tumor context in animal models of cancer. Modulators of Siglec function are likely to be developed and investigated clinically in a cancer context over the next few years.

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Section: Siglecs and The Capture Of Tumor‐derived Vesiclesmentioning

confidence: 98%

Section: Siglecs and The Capture Of Tumor‐derived Vesiclesmentioning

confidence: 99%

mentioning

confidence: 96%

mentioning

confidence: 99%

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Viewing Siglecs through the lens of tumor immunology

Fraschilla

Pillai

2017

Immunological Reviews

106

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“…Exosome samples (10 or 20 mg as stated) or OVA protein standard were boiled and reduced (except those for anti-CD138 probing) prior to gel electrophoresis and transferred to nitrocellulose membrane (9,21). Using 1% BSA/PBS as a blocker and diluent, we performed Western blotting of the membranes with goat polyclonal anti-milk fat globule-epidermal growth factor 8 (MFG-E8)-biotin (0.2 mg/ml; BAF2805; R&D Systems), rabbit polyclonal anti-14-3-3g (2 mg/ml; sc-731; Santa Cruz), mouse anti-Alix (2 mg/ml; clone 3A9, sc-53538; Santa Cruz), rat anti-CD138 (2 mg/ml; clone 281-2, 553712; BD), mouse anti-b-actin (0.5 mg/ml; clone AC-15; A1978; Sigma), or rabbit polyclonal anti-calnexin (2 mg/ml; sc-11397; Santa Cruz) or anti-OVA (5 mg/ml; 23744; Polysciences) Abs.…”

Section: Western Blottingmentioning

confidence: 99%

Role of Lymphocyte Subsets in the Immune Response to Primary B Cell–Derived Exosomes

Saunderson

McLellan

2017

The Journal of Immunology

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Exosomes are lipid nanovesicles released after fusion of the endosomal limiting membrane with the plasma membrane. In this study, we investigated the requirement for CD4 T cells, B cells, and NK cells to provide help for CD8 T cell-mediated response to B cell-derived exosomes. CTL responses to Ag-loaded exosomes were dependent on host MHC class I, with a critical role for splenic langerin CD8α dendritic cells (DCs) in exosomal Ag cross-presentation. In addition, there was an absolute dependence on the presence of CD4 T cells, CD8 T cells, and NK cells, where the loss of any one of these subsets led to a complete loss of CTL response. Interestingly, NK cell depletion experiments demonstrated a critical cutoff point for depletion efficacy, with low-level residual NK cells providing sufficient help to allow optimal CD8 T cell proliferative responses to exosomal protein. Despite the potential role for B cells in the response to B cell-derived exosomal proteins, B cell depletion did not alter the exosome-induced CTL response. Similarly, a possible role for the BCR or circulating Ab in mediating CTL responses to B cell-derived exosomes was ruled out using DLMP2A mice, which lack secreted and membrane-bound Ab, yet harbor marginal zone and follicular B cells. In contrast, CTL responses to DC-derived exosomes were significantly inhibited within Ab-deficient DLMP2A mice compared with wild-type mice. However, this response was not restored upon serum transfer, implicating a role for the BCR, but not circulating Ab, in DC-derived exosome responses.

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Melanoma‐derived extracellular vesicles mediate lymphatic remodelling and impair tumour immunity in draining lymph nodes

Leary

Walser

et al. 2022

J of Extracellular Vesicle

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Tumour-draining lymph nodes (LNs) undergo massive remodelling including expansion of the lymphatic sinuses, a process that has been linked to lymphatic metastasis by creation of a pre-metastatic niche. However, the signals leading to these changes have not been completely understood. Here, we found that extracellular vesicles (EVs) derived from melanoma cells are rapidly transported by lymphatic vessels to draining LNs, where they selectively interact with lymphatic endothelial cells (LECs) as well as medullary sinus macrophages. Interestingly, uptake of melanoma EVs by LNresident LECs was partly dependent on lymphatic VCAM-1 expression, and induced transcriptional changes as well as proliferation of those cells. Furthermore, melanoma EVs shuttled tumour antigens to LN LECs for cross-presentation on MHC-I, resulting in apoptosis induction in antigen-specific CD8 + T cells. In conclusion, our data identify EV-mediated melanoma-LN LEC communication as a new pathway involved in tumour progression and tumour immune inhibition, suggesting that EV uptake or effector mechanisms in LECs might represent a new target for melanoma therapy.

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The CD169 sialoadhesin molecule mediates cytotoxic T‐cell responses to tumour apoptotic vesicles

Cited by 30 publications

References 36 publications

Viewing Siglecs through the lens of tumor immunology

Viewing Siglecs through the lens of tumor immunology

Role of Lymphocyte Subsets in the Immune Response to Primary B Cell–Derived Exosomes

Melanoma‐derived extracellular vesicles mediate lymphatic remodelling and impair tumour immunity in draining lymph nodes

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