Gene Expression Profiling of Lymph Node Sub-Capsular Sinus Macrophages in Cancer
Lymph nodes are key lymphoid organs collecting lymph fluid and migratory cells from the tissue area they survey. When cancerous cells arise within a tissue, the sentinel lymph node is the first immunological organ to mount an immune response. Sub-capsular sinus macrophages (SSMs) are specialized mac...
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doaj-31eaaf388924471b98b16fbea5a41ebf2021-06-08T14:02:55ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-06-011210.3389/fimmu.2021.672123672123Gene Expression Profiling of Lymph Node Sub-Capsular Sinus Macrophages in CancerDanilo Pellin0Natalie Claudio1Natalie Claudio2Zihan Guo3Zihan Guo4Tahereh Ziglari5Ferdinando Pucci6Ferdinando Pucci7Gene Therapy Program, Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA, United StatesDepartment of Otolaryngology – Head and Neck Surgery, Oregon Health and Science University, Portland, OR, United StatesDepartment of Cell, Developmental & Cancer Biology, Oregon Health and Science University, Portland, OR, United StatesDepartment of Otolaryngology – Head and Neck Surgery, Oregon Health and Science University, Portland, OR, United StatesProgram in Cancer Biology, Oregon Health and Science University, Portland, OR, United StatesDepartment of Otolaryngology – Head and Neck Surgery, Oregon Health and Science University, Portland, OR, United StatesDepartment of Otolaryngology – Head and Neck Surgery, Oregon Health and Science University, Portland, OR, United StatesDepartment of Cell, Developmental & Cancer Biology, Oregon Health and Science University, Portland, OR, United StatesLymph nodes are key lymphoid organs collecting lymph fluid and migratory cells from the tissue area they survey. When cancerous cells arise within a tissue, the sentinel lymph node is the first immunological organ to mount an immune response. Sub-capsular sinus macrophages (SSMs) are specialized macrophages residing in the lymph nodes that play important roles as gatekeepers against particulate antigenic material. In the context of cancer, SSMs capture tumor-derived extracellular vesicles (tEVs), a form of particulate antigen released in high amounts by tumor cells. We and others have recently demonstrated that SSMs possess anti-tumor activity because in their absence tumors progress faster. A comprehensive profiling of SSMs represents an important first step to identify the cellular and molecular mechanisms responsible for SSM anti-tumor activity. Unfortunately, the isolation of SSMs for molecular analyses is very challenging. Here, we combined an optimized dissociation protocol, careful marker selection and stringent gating strategies to highly purify SSMs. We provide evidence of decreased T and B cell contamination, which allowed us to reveal the gene expression profile of this elusive macrophage subset. Squamous cell carcinomas induced an increase in the expression of Fc receptors, lysosomal and proteasomal enzymes in SSMs. Imaging of mouse and patient lymph nodes confirmed the presence of the top differentially expressed genes. These results suggest that SSMs respond to tumor formation by upregulating the machinery necessary for presentation of tumor particulate antigens to B cells.https://www.frontiersin.org/articles/10.3389/fimmu.2021.672123/fullcancerlymph nodesmacrophagesgene expressionimmune systemFc receptors |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Danilo Pellin Natalie Claudio Natalie Claudio Zihan Guo Zihan Guo Tahereh Ziglari Ferdinando Pucci Ferdinando Pucci |
spellingShingle |
Danilo Pellin Natalie Claudio Natalie Claudio Zihan Guo Zihan Guo Tahereh Ziglari Ferdinando Pucci Ferdinando Pucci Gene Expression Profiling of Lymph Node Sub-Capsular Sinus Macrophages in Cancer Frontiers in Immunology cancer lymph nodes macrophages gene expression immune system Fc receptors |
author_facet |
Danilo Pellin Natalie Claudio Natalie Claudio Zihan Guo Zihan Guo Tahereh Ziglari Ferdinando Pucci Ferdinando Pucci |
author_sort |
Danilo Pellin |
title |
Gene Expression Profiling of Lymph Node Sub-Capsular Sinus Macrophages in Cancer |
title_short |
Gene Expression Profiling of Lymph Node Sub-Capsular Sinus Macrophages in Cancer |
title_full |
Gene Expression Profiling of Lymph Node Sub-Capsular Sinus Macrophages in Cancer |
title_fullStr |
Gene Expression Profiling of Lymph Node Sub-Capsular Sinus Macrophages in Cancer |
title_full_unstemmed |
Gene Expression Profiling of Lymph Node Sub-Capsular Sinus Macrophages in Cancer |
title_sort |
gene expression profiling of lymph node sub-capsular sinus macrophages in cancer |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2021-06-01 |
description |
Lymph nodes are key lymphoid organs collecting lymph fluid and migratory cells from the tissue area they survey. When cancerous cells arise within a tissue, the sentinel lymph node is the first immunological organ to mount an immune response. Sub-capsular sinus macrophages (SSMs) are specialized macrophages residing in the lymph nodes that play important roles as gatekeepers against particulate antigenic material. In the context of cancer, SSMs capture tumor-derived extracellular vesicles (tEVs), a form of particulate antigen released in high amounts by tumor cells. We and others have recently demonstrated that SSMs possess anti-tumor activity because in their absence tumors progress faster. A comprehensive profiling of SSMs represents an important first step to identify the cellular and molecular mechanisms responsible for SSM anti-tumor activity. Unfortunately, the isolation of SSMs for molecular analyses is very challenging. Here, we combined an optimized dissociation protocol, careful marker selection and stringent gating strategies to highly purify SSMs. We provide evidence of decreased T and B cell contamination, which allowed us to reveal the gene expression profile of this elusive macrophage subset. Squamous cell carcinomas induced an increase in the expression of Fc receptors, lysosomal and proteasomal enzymes in SSMs. Imaging of mouse and patient lymph nodes confirmed the presence of the top differentially expressed genes. These results suggest that SSMs respond to tumor formation by upregulating the machinery necessary for presentation of tumor particulate antigens to B cells. |
topic |
cancer lymph nodes macrophages gene expression immune system Fc receptors |
url |
https://www.frontiersin.org/articles/10.3389/fimmu.2021.672123/full |
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