Anti-CD45RA Anticorpo [MEM-56] (FITC) (A86003)

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

Monoclonal antibodies against several human leucocyte cell surface antigens were prepared and characterized: (1) MEM-56, MEM-93, MEM-66, and MEM-104 against the CD45R antigen (220 kDa and 205 kDa mol. wt. forms of the leucocyte common antigen CD45 expressed on B-lymphocytes, myeloid cells and a subpopulation of T-lymphocytes); (2) MEM-98 and MEM-100 against the T-lymphocyte antigen CD6 (mol. wt. 100 kDa); (3) MEM-85 against the broadly expressed antigen CD44 (mol. wt. 85 kDa) which was recently shown by us to be identical with the lymphocyte homing receptor; (4) MEM-53 against a newly described broadly expressed antigen of 35-40 kDa mol. wt. and (5) MEM-102 against another newly described glycoprotein of 40 kDa mol. wt. anchored in membrane through a phosphatidylinositol moiety.