ICAM-1-LFA-1 Dependent CD8+ T-Lymphocyte Aggregation in Tumor Tissue Prevents Recirculation to Draining Lymph Nodes

Yanguas, Alba; Garasa, Saray; Teijeira, Álvaro; Aubá, Cristina; Melero, Ignacio; Rouzaut, Ana

doi:10.3389/fimmu.2018.02084

Cited by 37 publications

(22 citation statements)

References 52 publications

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“…In addition to T cell migration into tumors, T cells must also be able to recirculate from the tumor site to draining lymph nodes in order to mount distant responses (134). Interestingly, Yanguas et al showed that in a mouse model of melanoma, increased number of intra-tumorally injected tumor-specific T cells migrated into the draining lymph nodes in mice treated with anti-ICAM-1 or anti-LFA-1 mAbs compared to mice treated with control IgG (134). Further, activated T cells formed intra-tumoral clusters mediated by LFA-1/ICAM-1 interactions in mouse models of melanoma and breast cancer and similar T cell clusters were also visible in primary human melanoma.…”

Section: Introductionmentioning

confidence: 99%

Cell Adhesion Molecules and Their Roles and Regulation in the Immune and Tumor Microenvironment

et al. 2019

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The immune system and cancer have a complex relationship with the immune system playing a dual role in tumor development. The effector cells of the immune system can recognize and kill malignant cells while immune system-mediated inflammation can also promote tumor growth and regulatory cells suppress the anti-tumor responses. In the center of all anti-tumor responses is the ability of the immune cells to migrate to the tumor site and to interact with each other and with the malignant cells. Cell adhesion molecules including receptors of the immunoglobulin superfamily and integrins are of crucial importance in mediating these processes. Particularly integrins play a vital role in regulating all aspects of immune cell function including immune cell trafficking into tissues, effector cell activation and proliferation and the formation of the immunological synapse between immune cells or between immune cell and the target cell both during homeostasis and during inflammation and cancer. In this review we discuss the molecular mechanisms regulating integrin function and the role of integrins and other cell adhesion molecules in immune responses and in the tumor microenvironment. We also describe how malignant cells can utilize cell adhesion molecules to promote tumor growth and metastases and how these molecules could be targeted in cancer immunotherapy.

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Section: Introductionmentioning

confidence: 99%

Cell Adhesion Molecules and Their Roles and Regulation in the Immune and Tumor Microenvironment

et al. 2019

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“…Several studies indicated that ICAM-1 in the vascular endothelium was associated with T cell migration, and ICAM-1 expression was upregulated in lymphatic vessels and blood vessels in an inflammatory microenvironment, which promoted T cell migration and inflammatory responses [ 31 – 33 ]. Based on the inhibition of ICAM-1 expression mediated by miR-223, we further evaluated whether miR-223 could affect T cell migration.…”

Section: Resultsmentioning

confidence: 99%

Mesenchymal stem cell exosome-derived miR-223 alleviates acute graft-versus-host disease via reducing the migration of donor T cells

Liu¹,

Zhou

Liu³

et al. 2021

Stem Cell Res Ther

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Background Mesenchymal stem cells (MSCs) have been utilized in treating acute graft-versus-host disease (aGvHD) as they show strong immunosuppressive capacity through the release of various mediators, including immunosuppressive molecules, growth factors, chemokines, and exosomes. MicroRNAs (miRNAs) derived from MSC exosomes (MSCs-Exo) play a critical role in the regulation of immune responses. However, the function of miRNAs in treating aGvHD remains unknown. Here, we performed expression profiling of exosome-miRNAs from human umbilical cord MSCs (huc-MSCs) and murine compact bone MSCs (mb-MSCs) to investigate their immunoregulation effects in aGvHD. Methods Huc-MSCs-Exo and mb-MSCs-Exo were isolated and constructed MSCs-Exo-derived miRNA expression profiling using high-throughput sequencing. High expression of miR-223 was identified in both kinds of MSCs-Exo by bioinformatics analysis and quantitative real-time PCR (qPCR). In vitro cell crawling assay, transmigration assay and adhesion assay were subsequently applied to investigate the regulation of miR-223 on T cells. MiR-223 target gene was analyzed by western blot, luciferase analysis, and qPCR. Moreover, murine aGvHD model was established by infusing splenocytes and bone marrow nuclear cells from C57BL/6j mice (H-2Kb) into BALB/c recipient mice (H-2Kd). For therapeutic effect, MSCs or miR-223 Agomir were injected via tail vein. The general conditions of the mice in each group were monitored. Hematoxylin-eosin (H&E) staining was used to detect pathological changes of mice spleen, liver, and intestine. Mechanistically, immunofluorescence and flow cytometry were used to evaluate donor T cell migration, and enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of serum inflammatory cytokines IFN-γ, TNF-α, and IL-17. Results High-throughput sequencing revealed high expression of miR-223 in huc-MSCs-Exo and mb-MSCs-Exo. MiR-223 could restrain adhesion and migration of T cells by inhibiting ICAM-1 expression in mouse lymphatic endothelial cells. MiR-223Agomir infusion attenuated aGvHD clinical symptoms, reduced the donor T cell infiltration into the spleen, liver, and intestine, and decreased inflammatory cytokines IFN-γ, TNF-α, and IL-17. Conclusion MSCs-Exo-derived miR-223 could attenuate aGvHD in mice through decreasing donor T cell migration. Our results unveil a new role of MSCs-Exo containing miR-223 in the treatment of aGvHD.

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“…LFA-1 also interacts with intercellular adhesion molecules 1 (ICAM-1), which is related to cancer [6] . It was shown that disrupted LFA-1-ICAM-1 interaction in cancer models increases the presence of activated CD8+ T cells he incidence of tumor- draining lymph nodes [7] . Thus, LFA-1/ICAM-1 pathway plays an important role in in the protection from infections and cancer via activation and function of T cell trafficking [8] .…”

Section: Discussionmentioning

confidence: 99%

Investigation of LFA-1 rs2230433 variation in renal cell carcinoma tissues

Pençe¹

2019

Haydarpasa Numune Med J

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ICAM-1-LFA-1 Dependent CD8+ T-Lymphocyte Aggregation in Tumor Tissue Prevents Recirculation to Draining Lymph Nodes

Cited by 37 publications

References 52 publications

Cell Adhesion Molecules and Their Roles and Regulation in the Immune and Tumor Microenvironment

Cell Adhesion Molecules and Their Roles and Regulation in the Immune and Tumor Microenvironment

Mesenchymal stem cell exosome-derived miR-223 alleviates acute graft-versus-host disease via reducing the migration of donor T cells

Investigation of LFA-1 rs2230433 variation in renal cell carcinoma tissues

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