Early tumor effect on splenic Th lymphocytes in mice

European journal of cancer, 1979

V0rmal mice immunized with irradiated Ehrlich ascites tumor (EAT) cells rejected EAT challenge given 2 weeks later but T-cell-deficient [thymectomized lethally irradiated, and bone-marrow-reconstituted (TIR)] mice succumbed. However, when TIR mice were injected i.v. with thymus, lymph node, or spleen cells from normal syngeneic donors immediately following i.p. injection of irradiated EAT cells, they rejected the subsequent tumor challenge. This induction of immunity' in TIR mice was shown to be T-cell dependent. Spleen cells from EA T-&aring mice gicen immediately after irradiated tumor cells were also able to promote rejection of EAT challenge in TIR mice. Spleen cells from EAT-immune mice inhibited EAT growth when admixed with tumor cells prior to i.p. injection into normal recipients, but had no effect on progressive tumor growth when given i.v. immediately after i.p. tumor injection. Immune serum inhibited i.p. EAT growth when given either i.p. or i.e. Whereas inhibition of EAT growth by admixed sph'en cells was shown to be T-cell dependent, the activity of the immune serum appeared to be T-cell independent. The data indicate that T lymphocvtes are required only in the induction phase of the immune response of mice against EAT, while ~;he efferent phase of the response is accomplished @ serum antibodies, perhaps thro~'~gh an interaction with host macrophages.

Cancer Research, 1987

Thymostimulin (TS), a partially purified thymic factor, has a signifi cant impact on tumor development in C57B1/6 mice inoculated with Lewis lung carcinoma (3LL) cells, as judged by its effect on time of tumor appearance after tumor cell transplantation. In a previous study, we determined the conditions under which survival rate of the tumor-bearing mice can be significantly increased by TS treatment. In the study com municated here we analyzed host defense mechanisms that are modified by TS treatment in the tumor-bearing mice. In general, immune param eters that were increased or stimulated by the presence of the tumor were further increased in the TS-treated animals (number of lymphoid spleen cells, their response in mixed lymphocyte tumor cultures, their natural killer cell activity, and their ability to produce colony-stimulating factor), or reached earlier maximum levels (spontaneous [3H|thymidine incorpo ration, a reflection of in vivo spleen cell activation). Responses which reflect tumor-induced immunosuppression (proliferative response induced by phytohemagglutinin or concanavalin A stimulation) were restored to normal level by TS. Specific tumor-related reactions (specific cell-medi ated cytotoxicity) were preserved in the TS-treated animals. The wide spectrum of TS effects had, nevertheless, certain elements of selectivity; e.g. colony-stimulating factor, but no Interferon production is enhanced by TS in the tumor-bearing mice in diametric contrast to TS effect in Mengo virus-infected mice. The spectrum of TS effects was also depend ent on the type of tumor cell used. The results indicate that the significant effect of TS on 3LL tumor development in mice is associated with a strong, multifaceted effect of TS on the immune system.

European Journal of Immunology, 1973

were immunized in vitro against syngeneic HPC-108 plasma cell tumor cells.

Medicina, 2011

There is a rather generalized belief that the worst possible outcome for the application of immunological therapies against cancer is a null effect on tumor growth. However, a significant body of evidence summarized in the immunostimulatory hypothesis of cancer suggests that, upon certain circumstances, the growth of incipient and established tumors can be accelerated rather than inhibited by the immune response supposedly mounted to limit tumor growth. In order to provide more compelling evidence of this proposition, we have explored the growth behavior characteristics of twelve murine tumors -most of them of spontaneous origin- arisen in the colony of our laboratory, in putatively immunized and control mice. Using classical immunization procedures, 8 out of 12 tumors were actually stimulated in "immunized" mice while the remaining 4 were neither inhibited nor stimulated. Further, even these apparently non-antigenic tumors could reveal some antigenicity if more stringent ...

International Journal of Cancer, 1972

Circulating lymphocytes of rats carrying progressively growing polyoma tumors are specifically cytotoxic to polyoma tumor cells in vitro. The serum of such rats can block this lymphocyte cytotoxicity, an effect probably mediated by tumor-specific antigen-antibody complexes. Inoculation of blocking serum into rats has previously been shown to facilitate tumor growth. It is now demonstrated that so-called '' unblocking '' antibodies can be produced by immunization of BCG primed rats or rabbits with tumor cells. These antibodies can counteract the effect of specific blocking sera and tumor eluate in vitro. When inoculated into rats which had previously received a polyoma tumor isograft, unblocking serum was found to inhibit thcJ appearance of (or counteract) the blocking activity of serum in four of Jive rats. Tumors in these four rats grew progressively for 10-12 days and then compietely regressed. The effects of inociilation of unblocking scro into rats carrying primary kidney sarcomas, and subjected to splenectomy, were studied by in vitro tests for blocking and unblocking activity and for homologous complement-dependent cytotoxicity on serially-drawn serum samples from all treated rats, as well as for cytotoxicity of circulating lymphocytes fvom some of the animals. The serum blocking activity decreased or disappeared in all rats treated with unblocking serum while animals inoculated in parallel with control serum showed no such alteration. While sera of untreated rats or rats inoculated with control serum never had any detectable homologous complementdependent cytotoxic activity, such activity was demonstrated on several occasions in all tested rats inoculated with iinblocking sera. Unblocking activity was observed in several of the treated animals. Inoculating of unblocking sera from either rats or rabbits in combination with splenectomy led to the disappearance ofgrossly I>isible tumor in two rats and to retardation ofthe tumor growth rate in seven of nine other rats. The survival time of nine of I1 rats treated with unblocking sera was significantly prolonged. These results show that immiir~otlie~apetrtic effkcts can be whieved by serum treatment combined with splenecrorny. Although other mechanisms have riot been cxclutled, the I' vertical '' in vitro analysis of wrioics facets of the anti-tumor immune status of these animals supports the hypothc~sis that proceclwes cniintt~ractin~ thc blocking serum activity in vivo will allow the already present immune Iymphocytrs to exert their cytotoxic effect and thereby eliminate tumor cdls.

Immunity, 2001

Cancer Immunology Immunotherapy, 1989

Using a tumor-model system, differences in the accessory cell capabilities on autoreactive T cells of splenic macrophages from normal and tumor-bearing hosts (TBH) were assessed in the syngeneic mixed lymphocyte reaction. Tumor development caused a drop in autoreactivity. At 0 and 7 days of tumor growth, no drop in reactivity occurred when TBH macrophages were used as accessory cells and L3T4 + autoreactive T cells from normal mice were used as responder cells. However, by day 14, there was a 32% drop in reactivity, and by day 21 only 22% of the T cell reactivity remained when TBH macrophages were used as accessory cells. Alterations in macrophage Ia antigen during tumor growth were first investigated as the potential cause of reduced autoreactivity. Before tumor growth (day 0) 59% of the splenic macrophages were found to be Ia +. Day-7 TBH macrophages showed no difference in la antigen expression when compared to day0 macrophages. However, by day 14, TBH macrophages showed a 9% decrease, and by day 21 they showed a 36% decrease in the number which were Ia +. Concomitant with the decrease in the number of Ia + cells was a decrease in the density of Ia antigen expression on day-14 and -21 TBH macrophages. In day-14 and -21 TBH macrophages, two populations were seen that were Ia +. The first had a 10%-20% decrease in Ia antigen expression per cell while the second population had a >50% drop in Ia antigen expression per cell. By titrating and mixing TBH macrophages with normal host macrophages, we assessed whether they could actively mediate suppression of autoreactive T cells. A titratable suppressive phenomenon was demonstrated using day-21 TBH macrophages. In contrast, day-7 and -14 TBH macrophages titrated with normal host macrophages had no effect on the syngeneic mixed lymphocyte reactivity. Lastly, we investigated whether the macrophage-mediated suppression was caused by increased prostaglandin secretion. Addition of indomethacin to cultures increased autoreactive T cell reactivity stimulated by normal or TBH macrophages (59% and 99% increase, respectively). Although indomethacin reduced suppression mediated by TBH macrophages, autoreactivity did not return to levels induced by un-* This work was supported in part by an NIH Biomedical Research Support Grant and grants CA40009 and CA40010 Qffprint requests to: K. D. Elgert treated or indomethacin-treated cells from a normal host. Taken together, the data suggested that tumor growth modulates the function of macrophage accessory cells with autoreactive T cells in at least two ways: by decreasing Ia antigen expression and by increasing suppressor activity.

International Journal of Cancer, 1976

2012

Since the beginning of the nineteenth century, there have been reports about the possible involvement of the immune system in inhibiting of tumor growth. The starting point for research on tumor immunology is the fact that during malignant transformation each cell gains new antigenenic properties (different from the natural ones) which stimulates the immune system. Despite extensive knowledge, the role of the individual components of the immune system in hostneoplasm relationship is not fully specified. Its effectiveness is often inefficient because of tumor cells’ contrreaction, which in order to prevent tumor’s elimination by the host’s organism, evolved defensive reactions. Analysis of tumor growth at the level of cellular cytochemistry, determination of the disorders of the relationship between every stage of immune response, seems to be the basis for further understanding of the process of cancer’s development and progress. Intensive research in this field are carried out all o...

Cancer Immunology Immunotherapy, 1995

Human carcinoma cells vary appreciably in the expression of MHC class I, class II, ICAM-1 (CD54) and B7 (CD80) molecules. Short-term in vitro exposure of ex vivo carcinoma cells to interferon y and tumour necrosis factor ~ elevated/induced the surface expression of MHC class I, class lI and ICAM-1, but only rarely of B7. We found that cytokine treatment elevated the cytotoxic susceptibility and the stimulatory potential of ex vivo tumour cells. This was demonstrated (a) by the increased frequency and elevated level of auto-tumour lysis and (b) by induction of DNA synthesis and generation of cytotoxic lymphocytes in autologous mixed lymphocyte/tumour cell culture (MLTC). The MHC class I and ICAM-1 molecules on the tumour cells were required for interaction with the lymphocytes as indicated by the inhibitory effect of specific mAb both in the stimulation and in the cytotoxic tests. While the cytokine-induced increases in MHC and ICAM-1 on the low-expression tumours were probably important for the modification of functional interaction with the autologous lymphocytes, it is likely that alterations in other properties of tumour cells were also induced which contributed to the phe-nomenon. This was indicated by the results obtained with several tumours, which expressed indigenously high levels of these molecules but activated the autologous lymphocytes only after cytokine treatment.