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Myelopoiesis‐associated suppressor‐cell activity in mice with lewis lung carcinoma tumors: Interferon‐γ plus tumor necrosis factor‐α synergistically reduce suppressor cell activity
Author(s) -
Young M. Rita I.,
Young Melvin E.,
Wright Mark A.
Publication year - 1990
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910460217
Subject(s) - myelopoiesis , lewis lung carcinoma , tumor necrosis factor alpha , bone marrow , myeloid derived suppressor cell , cytotoxic t cell , cancer research , myeloid , immune system , progenitor cell , interferon , haematopoiesis , biology , spleen , immunology , medicine , stem cell , suppressor , in vitro , cancer , microbiology and biotechnology , metastasis , biochemistry
The myelopoietic stimulation which occurs in mice bearing metastatic Lewis lung carcinoma (LLC‐C3) tumors is accompanied by immune suppression and the appearance of myelopoiesis‐associated immune suppressor cells in the bone marrow and spleen. Low doses of recombinant murine interferon‐γ (IFN‐γ) plus recombinant human tumor necrosis factor‐α (TNF‐α) were used to limit myelopoiesis and, in turn, reduce the presence of myelopoiesis‐associated immune suppressor cells in LLC‐C3 tumor bearers. Neither IFN‐γ nor TNF‐α alone had any effect in vitro on the growth of myeloid progenitor cells into colonies or on the suppressive activity of bone‐marrow cells from LLC‐C3‐bearing mice. However, the combination of low doses of IFN‐γ and TNF‐α synergistically inhibited both the growth of myeloid progenitor cells into colonies and the suppressive activity of bone‐marrow cells from tumor‐bearers. Similar results were obtained in vivo. When used alone, neither IFN‐γ nor TNF‐α had any effect on myelopoiesis or on suppressor‐cell activity. When combined, IFN‐γ plus TNF‐α synergistically suppressed myelopoiesis and the presence of immune suppressive cells both in the bone marrow and in the spleen of tumor bearers. T‐lymphocyte blastogenic and NK cytotoxic activities of the tumor‐bearers were restored only after treatment with both IFN‐γ and TNF‐α.