Sequestration of Macrophages in Growing Tumours and its Effect on the Immunological Capacity of the Host

Abstract

Summary.-One hundred and sixteen human tumours were transplanted to thymectomized, irradiated, antilymphocyte serum-treated mice. In 12 cases the recipient mice died rapidly, presumably from infection. With the remaining 104 tumours, three-quarters grew to a varying extent, retaining the characteristic histological features of the primary tumours. Implant nodules varied widely in composition, from solid tumour and stroma to dense fibrous tissue without recognizable tumour cells. There was no relation between degree of malignancy and ability to grow, and also some benign tumours grew.In 44 cases, mice were treated with the drug or drugs most likely to be used in the patients and the effects on the implants were assessed histologically. Two tumours were largely destroyed and one showed marked metaphase arrest. Three other tumours showed lesser changes that were attributable to the drug but were of equivocal significance.There appeared to be differences in drug sensitivity between structurally different clones of the same tumour, and some tumours treated with two alkylating agents were damaged by one and not the other, suggesting that this model may have substantial discriminatory power. Assays such as this should not be used to guide treatment of the patient without prior validation. The practical and ethical difficulties of validation by clinical trial may be insurmountable, and an alternative approach to validation is proposed which does not raise these difficulties.

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

“…The experiments reported were carried out in the hope of elucidating the reasons for the differences in anti-inflammatory action of different sarcomata (Eccles and Alexander, 1974a (Whitelaw, 1966) and therefore to supply the monocytes entering the tumour, their output has to be vastly increased. The bone marrow is clearly capable of responding to this demand since the rat is not monocytopaenic but on the contrary the number of blood monocytes is raised by a factor of up to 8 although this does plateau, implying an upper limit of production.…”

“…IN a previous study (Eccles and Alexander, 1974a) syngeneic transplanted sarcomata were found to vary widely in the extent to which they reduced the capacity of rats to mount non-specific inflammatory reactions, as well as delayed hypersensitivity responses to antigens unrelated to the tumour. The former was measured by counting the number of macrophages recoverable from the peritoneal cavity 4 days after stimulation with oyster glycogen (in normal rats this produced an increase from 2 to 14 x 106 macrophages per rat).…”

Effects of the Landschütz ascites carcinoma and ascitic fluid on macrophage activity in C. parvum-injected mice

“…Clearly, a reduction in intensity of these changes would produce less marked hepatosplenomegaly, and indeed our histological observations confirm that this was the case. It may be argued that the reduction in cell proliferation and granuloma production could (Eccles & Alexander, 1974;Snyderman et al, 1975;Meltzer & Stevenson, 1977). In addition, key responses of macrophages, such as phagocytosis of opsonized red cells, chemotactic migration, bacterial resistance and their participation in anti-tumour immunity are affected by tumours or their extracts (Pike & Snyderman, 1976;Meltzer & Stevenson, 1977;Normann & Sorkin, 1976;North et al, 1978;.…”

Cancer and Subversion of Host Defences

“…As in human patients, a depressed capacity to express DTH has been found in rats and mice carrying any of a variety of tumours (Eccles and Alexander, 1974b;Wells et ai, 1974;Jessup et ai, 1976). DTH-like reactions induced in the foot by PHA were also suppressed (Wells et ai, 1974).…”