Splenectomy reduces lung metastases and tumoral and metastatic niche inflammation

• Verfasst von: Stöth, Manuel [VerfasserIn]
• Verfasst von: Freire Valls, Aida [VerfasserIn]
• Verfasst von: Chen, Mingyi [VerfasserIn]
• Verfasst von: Hidding, Sarah [VerfasserIn]
• Verfasst von: Knipper, Karl [VerfasserIn]
• Verfasst von: Shen, Ying [VerfasserIn]
• Verfasst von: Klose, Johannes [VerfasserIn]
• Verfasst von: Ulrich, Alexis [VerfasserIn]
• Verfasst von: Ruiz de Almodóvar, Carmen [VerfasserIn]
• Verfasst von: Schneider, Martin [VerfasserIn]
• Verfasst von: Schmidt, Thomas [VerfasserIn]
• Titel: Splenectomy reduces lung metastases and tumoral and metastatic niche inflammation
• Verf.angabe: Manuel Stöth, Aida Freire Valls, Mingyi Chen, Sarah Hidding, Karl Knipper, Ying Shen, Johannes Klose, Alexis Ulrich, Carmen Ruiz de Almodovar, Martin Schneider and Thomas Schmidt
• E-Jahr: 2019
• Jahr: 29 April 2019
• Umfang: 12 S.
• Fussnoten: Gesehen am 01.10.2019
• Titel Quelle: Enthalten in: International journal of cancer
• Ort Quelle: Malden, Mass. : Wiley-Blackwell, 1966
• Jahr Quelle: 2019
• Band/Heft Quelle: 145(2019), 9, Seite 2509-2520
• ISSN Quelle: 0020-7136
• DOI: doi:10.1002/ijc.32378
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: breast cancer
• Sach-SW: immune microenvironment
• Sach-SW: metastases
• Sach-SW: pre-metastatic niche
• Sach-SW: spleen
• K10plus-PPN: 1678017973

Abstract

The immune microenvironment plays a crucial role in supporting tumor growth and metastasis. Tumor-associated macrophages (TAMs) and neutrophils (TANs) are essential components of this microenvironment and affect tumor growth and progression in almost all solid neoplasms. Furthermore, TAMs, TANs and tumor-infiltrating dendritic cells (TIDCs) are found to infiltrate specific distant organs to prepare them as a site for metastatic cell seeding, forming the pre-metastatic niche. The spleen was identified as a major reservoir and source of circulating and tumor infiltrating immune cells. However, discrepancies about its role in supporting tumor growth exist. Thus, here we investigated the role of splenectomy in primary tumor and metastatic growth, and in the formation of an inflammatory niche. In a murine 4T1 and E0771 breast and Panc02 pancreatic cancer model, our results show that while splenectomy reduces the number of infiltrating TAMs, TANs and TIDCs within primary tumors, it does not affect its growth. In line, fewer TAMs, TANs and TIDCs accumulate in the metastatic microenvironment after splenectomy. Interestingly though, this affected metastatic growth depending on the metastatic route/site. The number of hematogenous breast cancer lung metastases was reduced after splenectomy but no effect was observed in breast or pancreatic lymph node metastases. Moreover, we observed that the immune composition of the pre-metastatic niche in lungs of breast cancer bearing mice was altered, and that this could cause the reduction of metastases. Altogether, our results highlight that splenectomy affects the immune microenvironment not only of primary tumors but also of pre-metastatic and metastatic sites.