Macrophage content of tumours in relation to metastatic spread and host immune reaction

Summary.-Cellular repopulation in Lewis carcinoma irradiated with 60Co y-rays was examined by performing sequential cell-survival estimations using an in vitro soft-agar-colony assay. Following local irradiation (15-35 Gy) two distinct types of colony were seen: compact colonies with tightly packed cells and diffuse colonies with widely dispersed cells. Maximal diffuse colony formation in vitro was only obtained in the simultaneous presence of adequate numbers of compact colonies. After wholebody irradiation only compact colonies were observed.Only cell-survival data from compact colony counts correlated with cell survival estimated by the lung colony assay and we conclude that compact colonies are produced by clonogenic tumour cells. Cytochemical and immunological evidence showed that diffuse colonies were composed of macrophages. After local irradiation the initial kill of clonogenic tumour cells was dose dependent. At each dose level, repopulation began immediately and proceeded with a doubling time of about 1 day. Macrophage colony-forming cells (macrophage progenitors) per tumour were initially reduced by about 3 decades, but recovered very rapidly to reach pretreatment levels within 2 days.We conclude that at least two populations of clonogenic cells are present in Lewis lung carcinoma, tumour cells that repopulate irradiated tumours by in situ proliferation and host-macrophage progenitors that repopulate locally irradiated tumours by infiltration. The hazards of confusing host and tumour cell colonies in in vitro assay systems are stressed.

Section: Discussionmentioning

confidence: 99%

Repopulation of γ-irradiated Lewis lung carcinoma by malignant cells and host macrophage progenitors

Stephens¹,

Currie²,

Peacock³

1978

“…Two other tumours, HSN and MC-1, with immunogenicities and metastatic capacities between those of HSBPA and MC-3 (Eccles and Alexander, 1974b), were also tested for their effects on monocyte levels at 10 days after inoculation, and the values obtained were 0-52 x 106 -and 0-46 x 106/ml respectively, which fall between the figures obtained for HSBPA and MC-3 at this stage of growth.…”

Section: Monocytosis Associated With Tumour Growthmentioning

confidence: 90%

Monocytosis associated with the growth of transplanted syngeneic rat sarcomata differing in immunogenicity

Eccles¹,

Bandlow²,

Alexander³

1976

Summary.-The effect of the growth of two syngeneic transplanted sarcomata of widely differing biological properties on the number of monocytes in the blood of rats was measured (1) by binding of a specific antimacrophage serum to leucocytes, and (2) by sedimenting in a density gradient rosettes between mononuclear cells and antibody-coated sheep red cells under conditions in which B-cells are not brought down. For the 4 syngeneic sarcomata studied there was a progressive increase in the number of monocytes with tumour growth and the values returned to normal a few days after their surgical removal. The extent of monocytosis was related to the immunogenicity of the tumour and was most pronounced for the HSBPA sarcoma, which is highly immunogenic, has a low rate of spontaneous metastasis and contains many macrophages, and least for the MC-3 sarcoma which is essentially non-immunogenic, invariably gives rise to distant metastases and contains only about 8% macrophages. The growth of sarcomata had previously been found to reduce the number of monocytes which enter inflammatory lesions, both non-specific and due to a delayed hypersensitivity reaction. This " antiinflammatory" action of sarcomata which is related to their immunogenicity cannot be ascribed to the preferential uptake of monocytes by the tumours and it is concluded that the monocytes in the blood of tumour-bearers, though increased in number, are modified so that they do not enter sites of inflammation.

“…In a series of rat sarcomas, the macrophage content was found to follow the immunogenicity of the different tumours, and ranged from less than 5% for non-immunogenic tumours to 50% of the total cell content in highly immunogenic sarcomas (Eccles & Alexander, 1974). In these sarcomas, macrophages were identified in cell suspensions obtained after trypsinization by a number of physiological tests, the simplest being their adherence to glass in the presence of trypsin.…”

Section: Infiltration Of the Tumour By Host Cellsmentioning

confidence: 99%

“…(i) The incidence of distant metastases is increased if the sarcomas are grown in rodents immunosuppressed by wholebody radiation (Eccles & Alexander, 1974), antilymphocyte serum (Fisher & Mannick, 1970) or selectively deprived of T cells (Eccles & Alexander, 1974, 1975.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Immunity as the predominant factor determining metastasis by murine lymphomas

Davey¹,

Currie²,

Alexander³

1979

Summary.-The metastatic behaviour of the L5178E (non-M) lymphoma and a highly metastatic subline L51787ES (M) were studied in syngeneic DBA2 mice. The non-M tumour rarely metastasizes in intact syngeneic mice, but produces extensive and rapidly lethal metastases when implanted into irradiated recipients. The metastatic behaviour of the M subline is unaffected by irradiation of the host. By conventional transplantation criteria, the non-M tumour is more immunogenic than the M subline. Both tumours, however, produce similar responses in a lymphnode weightgain assay. Host-cell infiltration of the tumours growing s.c. is much greater in the non-M than the M, the infiltrating cells being Fc-receptor-positive and maturing into macrophages after 2 days in vitro.Although spontaneous in vitro motility of the M cells is much greater than that of the non-M, the metastatic behaviour of the tumours is clearly determined by host immunological responses.