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- W4225371211 abstract "Metastasis remains the principal cause of cancer mortality. Lymph node metastases are common and indicate poor overall prognosis, likely due to both the metastatic potential of primary tumor cells and the contribution of lymph node metastases to distant metastases. Although antitumor T cells are generated in lymph nodes, metastatic cancer cells are able to grow in this seemingly hostile microenvironment. We hypothesized that lymph node metastases actively suppress anti-tumor responses in lymph nodes. The overall goal of our study is to understand how cancer cells avoid immune detection in lymph nodes. We obtained patient samples, established a novel ER+ mammary carcinoma (MCa) cell line and employed 4T1 triple negative breast cancer cells to investigate the growth of spontaneous lymphatic metastases. In addition, we developed a lymph node compression apparatus to mimic the compressive forces, known as solid stress, generated by cancer cells in lymph nodes. We used immunofluorescence microscopy, intravital imaging, flow cytometry, and quantitative PCR to characterize the effect of cancer growth on adaptive immune responses in tumor-involved lymph nodes. Using patient tissue from multiple cancers and preclinical models of spontaneous lymph node metastases, we show that cancer cells disrupt lymphocyte trafficking to lymph nodes, resulting in exclusion of lymphocytes from metastatic lesions. The presence of solid stress caused by lesion growth is associated with a reduction of functional blood vessels and lymphocyte exclusion in the nodes. Relieving solid stress in the mice increased the presence of lymphocytes in lymph node lesions. These findings reveal a novel mechanism for the lack of immune response against lymph node metastases and may inform strategies for immunotherapy." @default.
- W4225371211 created "2022-05-05" @default.
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- W4225371211 date "2022-05-01" @default.
- W4225371211 modified "2023-09-27" @default.
- W4225371211 title "Solid stress impairs lymphocyte infiltration into lymph node metastases" @default.
- W4225371211 doi "https://doi.org/10.1096/fasebj.2022.36.s1.r4616" @default.
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