Prognostic Significance of CD169+ Lymph Node Sinus Macrophages in Patients with Malignant Melanoma

Saito, Yoichi; Ohnishi, Koji; Miyashita, Azusa; Nakahara, Shiro; Fujiwara, Yukio; Horlad, Hasita; Motoshima, Takanobu; Fukushima, Satoshi; Jinnin, Masatoshi; Ihn, Hironobu; Takeya, Motohiro; Komohara, Yoshihiro

doi:10.1158/2326-6066.cir-14-0180

Cited by 66 publications

(96 citation statements)

References 26 publications

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“…19 Similar observations were subsequently observed in patients with melanoma, endometrial cancer, and breast cancer. [25][26][27][28] A number of methods for targeting antigens to LN macrophages have been investigated as part of the ongoing development of lymphatic-targeted vaccines. It was reported that cholesteryl pullulan (CHP) nanogels induce tumor regression in some patients with malignant tumors, 29,30 and CD169-positive macrophages in LN sinus captured CHP nanogels and worked as APCs.…”

Section: Discussionmentioning

confidence: 99%

Natural compounds that regulate lymph node sinus macrophages: Inducing an anti-tumor effect by regulating macrophage activation

Fujiwara

Saito

Shiota

et al. 2018

JCEH

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Section: Discussionmentioning

confidence: 99%

Natural compounds that regulate lymph node sinus macrophages: Inducing an anti-tumor effect by regulating macrophage activation

Fujiwara

Saito

Shiota

et al. 2018

JCEH

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“…administration of iPS-ML-IFNa cells could decrease the number of endogenous M2 macrophages. We have recently reported that melanoma-bearing patients, especially those with recurrence, have few M1-type macrophages in their regional lymph nodes (19). It therefore makes sense to supply melanoma patients with iPS-ML cells that produce type I IFNs (M1 macrophage-like cells).…”

Section: Accumulation and Infiltration Of Ips-ml In Established Tumormentioning

confidence: 99%

Immunotherapy against Metastatic Melanoma with Human iPS Cell–Derived Myeloid Cell Lines Producing Type I Interferons

Miyashita

Fukushima

Nakahara

et al. 2016

Cancer Immunology Research

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In recent years, immunotherapy for advanced melanoma has been gaining increased attention. The efficacy of anti-cytotoxic T-lymphocyte antigen 4 antibodies, anti-programmed cell death 1 antibodies, and the BRAF V600E kinase inhibitor has been proven in metastatic melanoma. At the same time, adoptive cell transfer has significant effects against metastatic melanoma; however, it is difficult to apply on a broad scale because of the problems related to cell preparation. To overcome these problems, we developed immune cell therapy using induced pluripotent stem (iPS) cells. The benefit of our method is that a large number of cells can be readily obtained. We focused on macrophages for immune cell therapy because macrophage infiltration is frequently observed in solid cancers. In this study, the efficacy of human iPS cell-derived myeloid cell lines (iPS-ML) genetically modified to express type I IFNs against human melanoma cells was examined. The morphology, phagocytic ability, and surface markers of iPS-ML were similar to those of macrophages. The iPS-ML that express type I IFNs (iPS-ML-IFN) showed significant effects in inhibiting the growth of disseminated human melanoma cells in SCID mice. The infiltration of iPS-ML into the tumor nests was confirmed immunohistologically. The iPS-ML-IFNs increased the expression of CD169, a marker of M1 macrophages that can activate antitumor immunity. The iPS-ML-IFNs could infiltrate into tumor tissue and exert anticancer effects in the local tumor tissue. In conclusion, this method will provide a new therapeutic modality for metastatic melanoma.

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“…Consistent with previous reports, CD169 protein was mainly expressed on CD68 C Mf in the LN sinus. 27,35 Interestingly, multi-staining confocal microscopy analysis revealed a certain proportion of CD169 C cells were CD3 C CD8 C T cells (Fig. 1A and S2).…”

Section: Cd169 C Cd8 C T Cells Accumulate In Regional Ln and Decreasementioning

confidence: 96%

CD169 identifies an activated CD8⁺T cell subset in regional lymph nodes that predicts favorable prognosis in colorectal cancer patients

Zhang

et al. 2016

OncoImmunology

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Purpose: CD169 was first identified on macrophages (Mf) and linked to antigen presentation. Here, we showed CD169 expression on some CD8 C T lymphocytes in regional lymph nodes (LNs) and investigated the function and clinical relevance of CD169 C CD8 C T cells in tumor-draining LNs of colorectal cancer (CRC) patients. Experimental design: Fresh tumor-draining LN tissues from 39 randomly enrolled patients were assessed by flow cytometry for activation and differentiation of CD169 C CD8 C T cells and T cell-mediated killing of tumor cells. In total, 114 tumor-draining LN paraffin sections from CRC patients were analyzed by multiplecolor immunofluorescence for CD169 C CD8 C T cell distribution and clinical values. The prognostic significance of CD169 C CD8 C T cells was evaluated by Kaplan-Meier analysis. Results: A fraction of CD8 C T cells in regional LNs, but not peripheral blood, tonsils, or tumors, expressed surface CD169. In situ detection of draining LNs revealed preferential localization of CD169 C CD8 C T cells to subcapsular sinus and interfollicular regions, closely associated with CD169 C Mf. CD169 C CD8 C T cell ratios were significantly lower in peri-tumor LNs than distant-tumor LNs. CD169 C CD8 C T cells predominantly expressed activation markers (CD69, HLA-DR, PD-1) with slightly lower CD45RA and CD62L levels. They produced high granzyme B, perforin, TNF-a, and IFNg levels, and promoted tumor-killing efficiency ex vitro. Moreover, CD169 C CD8 C T cells infiltrating tumor-draining LNs decreased with disease progression and were strongly associated with CRC patient survival. Conclusions: We identified novel activated/cytolytic CD169 C CD8 C T cells selectively present in regional LNs, potentially serving as a powerful prognostic factor and indicator for selecting patients for immunotherapy.

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Prognostic Significance of CD169+ Lymph Node Sinus Macrophages in Patients with Malignant Melanoma

Abstract: These data suggest that IFNa-stimulated CD169 þ macrophages inRLNs are closely involved in T-cell-mediated antitumor immunity and may be a useful marker for assessing the clinical prognosis and monitoring antitumor immunity in patients with malignant melanoma.

Cited by 66 publications

References 26 publications

Natural compounds that regulate lymph node sinus macrophages: Inducing an anti-tumor effect by regulating macrophage activation

Natural compounds that regulate lymph node sinus macrophages: Inducing an anti-tumor effect by regulating macrophage activation

Immunotherapy against Metastatic Melanoma with Human iPS Cell–Derived Myeloid Cell Lines Producing Type I Interferons

CD169 identifies an activated CD8⁺T cell subset in regional lymph nodes that predicts favorable prognosis in colorectal cancer patients

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Prognostic Significance of CD169+ Lymph Node Sinus Macrophages in Patients with Malignant Melanoma

Abstract: These data suggest that IFNa-stimulated CD169 þ macrophages inRLNs are closely involved in T-cell-mediated antitumor immunity and may be a useful marker for assessing the clinical prognosis and monitoring antitumor immunity in patients with malignant melanoma.

Cited by 66 publications

References 26 publications

Natural compounds that regulate lymph node sinus macrophages: Inducing an anti-tumor effect by regulating macrophage activation

Natural compounds that regulate lymph node sinus macrophages: Inducing an anti-tumor effect by regulating macrophage activation

Immunotherapy against Metastatic Melanoma with Human iPS Cell–Derived Myeloid Cell Lines Producing Type I Interferons

CD169 identifies an activated CD8+T cell subset in regional lymph nodes that predicts favorable prognosis in colorectal cancer patients

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CD169 identifies an activated CD8⁺T cell subset in regional lymph nodes that predicts favorable prognosis in colorectal cancer patients