Coexistence of immunogenic and suppressogenic epitopes in tumor cells and various types of macromolecules

Naor, David

doi:10.1007/bf00199898

Cited by 28 publications

(9 citation statements)

References 65 publications

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“…The coexistence of immunogenic and immunosuppressive antigens in the same tumor has been previously reported (reviewed in Naor, 1983;Urban et al, 1984). The interactions between TR and TS cells suggest that some tumor cell subpopulations bear predominantly immunosuppressive determinants while others bear predominantly immunogenic determinants.…”

Section: Al 1976)mentioning

confidence: 84%

Interaction between two cellular subpopulations of a rat colonic carcinoma when inoculated to the syngeneic host

Caignard

Martin

Michel

et al. 1985

Intl Journal of Cancer

111

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From a single, chemically-induced rat colonic carcinoma, two subpopulations of tumor cells have been isolated. When injected into syngeneic rats, TR cells give rise to progressive tumors in most of the animals, whereas TS cells give rise to no tumors or to tumors which regress in less than 30 days. TS cells inhibit the growth of TR tumors, whether they are injected before TR cells or simultaneously, at a different site or mixed with the TR cells. Lymph nodes and spleen lymphocytes from animals having rejected TS tumors also inhibit TR-cell growth. On the other hand, TS cells are able to give rise to progressive tumors when they are injected into rats bearing established TR tumors. Lymph nodes and spleen cells of TR tumor-bearing rats are able to enhance TS cell growth. These results suggest that subpopulations of cancer cells contained in the same tumor interact with each other through their effect on the host immune system. The growth of a whole tumor probably depends not only on the growth potential of each constituent subpopulation, but also on the interaction between the subpopulations themselves.

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Section: Al 1976)mentioning

confidence: 84%

Interaction between two cellular subpopulations of a rat colonic carcinoma when inoculated to the syngeneic host

Caignard

Martin

Michel

et al. 1985

Intl Journal of Cancer

111

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“…It is possible that the superiority of L-PAM to mitomycin C in the generation of immunostimulatory tumor cells reflects a differential in drug-influenced alteration in the antigen shedding process and/or in cellular stability. Still, these results demonstrate that L-PAM-induced potentiation of tumor cell immunostimulatory activity is not merely the result of reduction in tumor cell proliferative capacity, but probably also the result of intrinsic alteration(s) in the tumor cell which may modify antigen presentation [11] and/or production of helper or suppressor factors [30,31,38] so as to elicit the generation of potent T-cell-dependent antitumor immunity.…”

Section: Discussionmentioning

confidence: 99%

Melphalan-induced enhancement of tumor cell immunostimulatory capacity as a mechanism for the appearance of potent antitumor immunity in the spleen of mice bearing a large metastatic MOPC-315 tumor

Bocian

Dray

Ben-Efraim

et al. 1985

Cancer Immunol Immunother

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Exposure of MOPC-315 cells from the primary tumor nodule to a low concentration (0.5 nmol/ml) of melphalan (L-phenylalanine mustard; L-PAM) rendered the tumor cells capable of bringing about the generation of a potent primary antitumor cytotoxic response. Accordingly, the level of antitumor cytotoxicity generated by normal spleen cells immunized in vitro with L-PAm-treated tumor cells was at least five-fold greater than the level generated in response to untreated tumor cells. The marked superiority of L-PAM-treated tumor cells over untreated tumor cells in bringing about the generation of antitumor cytotoxicity was evident over a wide range of responder to stimulator cell ratios. The higher level of antitumor cytotoxicity exhibited by normal spleen cells immunized with L-PAM-treated tumor cells as compared with untreated tumor cells was not merely the result of direct drug-mediated tumoricidal activity, thereby reducing the number of tumor cells present which can act as cold target cell inhibitors during the 51Cr release assay. This is apparent from the observation that the level of antitumor cytotoxicity generated in response to a given percentage of stimulator tumor cells pretreated with 0.5 nmol L-PAM/ml, a drug concentration associated with retention of 60% tumor cell proliferative capacity, is substantially greater than that generated in response to less than half that percentage of untreated stimulator tumor cells. Moreover, stimulator tumor cells exposed to a fully antiproliferative concentration of L-PAM brought about the generation of a higher level of antitumor cytotoxicity than stimulator tumor cells exposed to mitomycin C at a concentration which inhibited the proliferation of the tumor cells to the same extent as the L-PAM. A low concentration of L-PAM which was effective in rendering isolated tumor cells from the primary tumor nodule capable of bringing about the generation of antitumor cytotoxicity was also effective in inducing the appearance of potent antitumor immune potential in tumor bearer splenic cells containing metastatic tumor cells.

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“…As shown in Figure 4 well; in fact, it has been shown that DR antigens play a crucial role in antigen presentation (77) as well as ioithe activation of specific helper or suppressor lymphocytes (78). It may also be possible that DR antigens on Auto-Me cells can function as restriction elements for the recognition of immunogenic or suppressogenic entities specifically expressed on primary or metastatic cells (94). Alternatively, different products of HLA-D region may be present on primary or metastatic cells each of which can preferentially induce either stimulation or inhibition of Pt-PBL responses.…”

Section: B Correlation Between Dr Antigen Expression On Metastatic Mmentioning

confidence: 99%

Autologous cellular immune response to primary and metastatic human melanomas and its regulation by DR antigens expressed on tumor cells

et al. 1985

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Evidence for heterogeneity of several biological features of human malignant melanoma (Me) like morphology, cytogenetics, oncogenes activation, antigenic expression, metastatizing capacity and procoagulant activity are briefly reviewed in an attempt to distinguish findings related to primary vs. metastatic lesions. In our own studies monoclonal antibodies were used to study expression of MHC class I, class II products and of Me-associated antigens (MAA) on primary and metastatic Me cells. High expression of class I antigens was found in a high percentage of both primary and metastatic tumors, whereas DR and MAA showed a significant variation (from 3 to 90% of cells) in expression both in primary and in metastatic Me. When autologous cell-mediated immune responses were evaluated, it was found that Me cells from primary tumors but not those from lymph node metastases were able to stimulate autologous lymphocytes to proliferate and become cytotoxic for autologous Me. Clonal analysis of cytotoxic lymphocytes was then carried out in order to see whether the lack of lymphocytes reactivity to metastatic cells was due to the absence or to a low frequency of cytotoxic cells in the unstimulated PBL. CTL clones cytotoxic for autologous Me (Auto-Me) cells were indeed isolated. Three classes of CTL clones were identified: 1) one which is cytotoxic for Auto-Me; 2) a second one which lyse Auto-Me and allogeneic Me; and 3) a third one which is cytotoxic for Auto-Me and allogeneic normal and neoplastic cells. Metastatic Me cells, however, had the ability to suppress the stimulation of autologous PBL by alloantigens or IL-2. This effect was dose-dependent and was not due to absorption of IL-2 by Me cells. Since it has been reported that Me cells express class II MHC antigens, we investigated whether there was any correlation between autologous immune responses and DR expression on Me cells. Autologous lymphocytes stimulation was found to occur only with DR+ Me cells from primary lesions, whereas metastatic cells, either DR+ or DR-, did not stimulate autologous PBL. Moreover, the suppressive effect of metastatic Me cells was associated with their expression of DR antigens. The modulation of DR antigens on Me cells by Interferon-gamma correlated positively with their suppressive capacity. Thus, it appears that primary Me can behave differently from the metastatic one in their interactions with the immune system of autologous host. These findings suggest that DR antigens on Me cells may have an important role in the regulation of autologous immune responses.

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Coexistence of immunogenic and suppressogenic epitopes in tumor cells and various types of macromolecules

Cited by 28 publications

References 65 publications

Interaction between two cellular subpopulations of a rat colonic carcinoma when inoculated to the syngeneic host

Interaction between two cellular subpopulations of a rat colonic carcinoma when inoculated to the syngeneic host

Melphalan-induced enhancement of tumor cell immunostimulatory capacity as a mechanism for the appearance of potent antitumor immunity in the spleen of mice bearing a large metastatic MOPC-315 tumor

Autologous cellular immune response to primary and metastatic human melanomas and its regulation by DR antigens expressed on tumor cells

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