The development of cellular immunity to a syngeneic squamous cell carcinoma in Wistar rats was studied by
in vitro
microcytotoxicity assay. Reactivity of lymphocytes from lymph nodes, spleen and blood was tested throughout the period of tumour growth. Maximum lymphocyte cytotoxicity against the tumour was observed at 2 weeks in regional lymph nodes, 4 weeks in intermediate nodes, spleen and blood, and 6 weeks in distant nodes; the intensity of these cytotoxic responses subsequently declined. In the regional nodes, lymphocytes became totally unresponsive despite the maintenance of significant cytotoxicity in intermediate nodes, spleen and blood. Local anergy may account for tumour spread to the regional node in an otherwise immunocompetent host. This anergy may be due to high local concentration of tumour antigen or antigen-antibody complexes, but it was not associated with selective changes in T and B cell proportions.
Summary.-The development of serum factors by Wistar rats during the growth of a syngeneic squamous cell carcinoma has been investigated to clarify the nature of the local lymphocyte anergy reported previously in this system. Sera from tumour bearing animals were tested for cytotoxicity against tumour cells by in vitro microassay, and their ability to inhibit cell mediated cytotoxicity was also studied. Serum cytotoxicity was first detected after 2 weeks of tumour growth, reaching a peak at 4 weeks and then declining. Inhibitory activity was found only in the sera of animals with advanced tumours. Anti-tumour antibody either in the sera or bound-to tumour cells was not detected by immunofluorescence techniques. No evidence of general immunological debilitation was found, the animals showing normal immune responses to sheep erythrocytes and killed Brucella abortus organisms throughout tumour growth. Serum inhibitory factors may be responsible for the decline in antitumour immunoreactivity and the local lymphocyte anergy observed in tumour bearing hosts.
Summary.-Splenocytes from inbred Wistar rats bearing a syngeneic squamous cell carcinoma (Spl) were fractionated by several techniques to characterize the lymphoid cells cytotoxic to the tumour in vitro. The anti-tumour cytotoxicity is presumably mediated primarily by T lymphocytes because it was greatly reduced by removal of T lymphocytes with heterologous anti-T serum plus complement but not by removal of other cell types. Cytotoxicity could be blocked at the tumour cell but not at the effector cell by sera taken late in tumour growth. Sera taken earlier in tumour growth could induce cytolysis of tumour cells by normal splenocytes but only if the tumour cells were treated with serum and washed before addition of the effector cells. Although splenocytes from normal and tumour-bearing rats were equally effective at lysing antibody-coated target cells it is unlikely that this mechanism is important in vivo as sera from early in tumour growth onwards contained factors (immune complexes?) which inhibited antibody-induced lymphocytolysis.*
It has been observed that in human breast cancer transposition of the greater omentum to cover the excision site after removal of recurrent tumor appears to inhibit further recurrences at the site, without affecting spread to other sites. To establish an experimental model of this, inbred rats were transplanted in two sites on the chest with pieces of either an epithelioma or a mammary tumor. A flap of the omentum was then drawn through the peritoneal wall and then secured over one of the implants. In one group, this omentoplasty was carried out 1 week after tumor implantation. In most rats, the tumor in contact with the omentum was actually larger than the control, in contrast to the clinical observations. In many animals, the omentum was also a route of metastasis of the tumor.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.