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Involvement of Macrophage-like Cells in Growth of Tumors Induced by Avian Sarcoma Virus¹

Lady Davis Institute for Medical Research of the Sir Mortimer B. Davis-Jewish General Hospital, Montreal H3T 1E2 [M. A. W., B. B., H. F., S.B.]; Department of Microbiology and Immunology, McGill University, Montreal H3T 2T5 [M. A. W.]; and Laboratory of Immunovirology, Pediatric Research Center, Sainte Justine Hospital, Montreal H3T 1C5 [J. M.], Quebec, Canada

We have investigated the mechanism(s) whereby the s.c. injection of Bacillus Calmette-Guérin (BCG) into chicken wing webs, 7 days prior to inoculation with avian sarcoma virus (ASV) at the same site, can dramatically stimulate the growth of ASV-induced tumors. The results show that neoplasms induced in this fashion contain a much higher percentage of macrophage-like cells than do those induced by ASV alone. These macrophage-like cells have been identified on the basis of adherence properties and their abilities to phagocytose red blood cells, to express Fc receptors at their surface, and to express nonspecific esterase activity. They are apparently infected by ASV, and both produce progeny virus in culture and express viral antigens at their surface. Inoculation of such cells into chickens leads to tumor development, indicating that they can produce ASV in vivo as well as in vitro. The macrophage-like cells in question are present most predominantly during the earliest stages of ASV-induced tumor growth and can survive in tissue culture over long periods. Although pretreatment with BCG at sites other than that used for ASV inoculation had no effect on tumor growth, the administration of BCG at any site was stimulatory to the development of antitumor immunity. This was obviously of little avail in the case of animals developing tumors resulting from the BCG enhancement effect. We conclude that pretreatment with BCG, under the circumstances tested, gives rise to an acute granulomatous reaction which provides large numbers of target cells for transformation by ASV administered at the same site. Many of these cells are macrophages which provide a reservoir for continuous virus production in the face of an antitumor immune response. Macrophage-like cells are also present in tumors which arise following inoculation by ASV alone, but to an extent apparently insufficient to permit irreversible tumor growth.

¹ Supported by the National Cancer Institute of Canada and by the Claire and Sam Bell Endowment Fund for Cancer Research.

² Research associate of the Conseil de la Recherche en Santé du Québec. To whom requests for reprints should be addressed, at the Lady Davis Institute, Jewish General Hospital, 3755 Cote Ste-Catherine Road, Montreal, Quebec, Canada H3T 1E2.

Received 8/26/82. Accepted 1/ 6/83.