Hematopoiesis and suppressor bone marrow cells in mice bearing large metastatic Lewis lung carcinoma tumors

Abstract

Mice bearing a metastatic variant of Lewis lung carcinoma (LLC-C3) were studied to determine if there might be a relationship between tumor induced hematopoiesis and immune suppression. Growth of LLC-C3 in C57BL/6 mice corresponded with increased hematopoiesis and an increase in the proportion of monocytes in the peripheral blood, spleen, and bone marrow. The LLC-C3 cells secreted colony stimulating factor activity and, thus, could have directly stimulated the hematopoiesis in the hosts. As tumor growth progressed, the bone marrow of the tumor bearing mice became suppressive to T-cell blastogenesis. The bone marrow suppressor cells obtained from mice bearing large (greater than 3 g) LLC-C3 tumors were nonadherent to nylon wool, sensitive to treatment with L-leucine methyl ester, insensitive to treatment with anti-Thy-1.2 and complement, and mediated their suppression through an indomethacin sensitive mechanism. Secretion of colony stimulating factor activity by the LLC-C3 cells could have induced the appearance of the bone marrow suppressor cells since normal bone marrow cells which were cultured in the presence of LLC-C3 culture supernatants had an increased proportion of monocytes and were suppressive to T-lymphocyte blastogenesis. Our results suggest that the colony stimulating factor activity produced by LLC-C3 cells stimulates hematopoiesis which, in turn, could result in the appearance of bone marrow suppressor cells.