Origins of tumor-associated macrophages and neutrophils

• DOI: 10.1073/pnas.1113744109
• Publication Date: 2012-01-31T06:24:54Z
• Authors: Virna Cortez-Reta...; Martin Etzrodt; Andita Newton; Philipp J. Rauch; Aleksey Chudnovskiy; Cedric Berger; Russell J. H. Ryan; Yoshiko Iwamoto; Brett Marinelli; Rostic Gorbatov; Reza Forghani; Tatiana I. Novobr...; Victor Koteliansky; Jose-Luiz Figueiredo; John W. Chen; Daniel G. Anderson; Matthias Nahrendorf; Filip K. Swirski; Ralph Weissleder; Mikael J. Pittet
• Keywords: Red pulp; Extramedullary hematopoiesis; White pulp; Monocyte

Tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs) can control cancer growth exist in almost all solid neoplasms. The cells are known to descend from immature monocytic granulocytic cells, respectively, which produced the bone marrow. However, spleen is also a recently identified reservoir of monocytes, play significant role inflammatory response that follows acute injury. Here, we evaluated splenic genetic mouse model lung adenocarcinoma driven by activation oncogenic Kras inactivation p53. We found high numbers TAM TAN precursors physically relocated tumor stroma, recruitment tumor-promoting spleen-derived TAMs required signaling chemokine receptor CCR2. Also, removal spleen, either before or after initiation, reduced responses significantly delayed growth. mechanism was able maintain its capacity throughout progression involved, part, local accumulation red pulp typically rare extramedullary hematopoietic stem progenitor notably granulocyte macrophage progenitors, CD11b + Ly-6C hi Ly-6G locally. Splenic progenitors their descendants were likewise clinical specimens. present study sheds light on origins TANs, positions as an important site, continuously supply growing tumors with these cells.