DR antigens expressed on tumor cells do not contribute to the blastogenetic response of autologous T cells

Vánky, Farkas; Klein, Eva; Willems, Jan

doi:10.1007/bf00199230

Cited by 25 publications

(9 citation statements)

References 23 publications

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“…A role for class II antigens, especially DR, emerges from our studies which suggest that DR expressed on Me cells can regulate both positively and negatively the cellular immune response of the patients. These data seem to be confirmed by some studies (51) but not by others (91). It is important to further define the function of DR molecules in the regulation of the immune interactions between the tumor and the host and to identify which molecule (DR DC, SB) and epitopes may have such regulatory function.…”

Section: Discussionsupporting

confidence: 48%

“…Moreover, these authors stressed the correlation between DR expression and positive MLTC by using FACS-isolated DR+ cells, which did stimulate much more than DR-cells derived from the same Me cell population. However, other recent results did not support a positive correlation between the expression of DR antigens on human tumors of different histology and autologous MLTC (91).…”

Section: A Correlation Between Class H Antigens Expression On Primarmentioning

confidence: 62%

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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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Section: Discussionsupporting

confidence: 48%

Section: A Correlation Between Class H Antigens Expression On Primarmentioning

confidence: 62%

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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“…Nevertheless the induction of lymphocyte proliferation and cytotoxicity has to date proved useful in identifying cross-reacting antigens in human neoplasms and in the disclosure of effector cells with variable target cell repertoires [31]. Moreover, there is a correlation between lymphocyte-mediated auto-tumour reactivity and clinical course [29,30].…”

Section: Introductionmentioning

confidence: 97%

Proliferative and cytotoxic responses of human peripheral blood lymphocytes to autologous malignant effusions

Roberts

Shipton

Moore

1986

Cancer Immunol Immunother

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Peripheral blood lymphocytes from five patients were stimulated initially in mixed lymphocyte:tumour culture (MLTC) with autologous malignant effusions and cloned by limiting dilution in interleukin-2 prior to phenotyping and assay for different functional capabilities namely proliferative responsiveness to autologous and allogeneic tumours in the primed lymphocyte test (PLT) and cytotoxicity (CTX) toward a range of fresh tumour and cell line targets. For individual clones the two functional activities tended to be mutually exclusive. Clones (or 'cloids' containing more than one PLT precursor) from three of four tumours analysed were responsive to autologous tumour cells in the PLT of which two shared antigens with allogeneic tumours of similar tissue provenance. All phenotyped PLT positive clones were T3+T4+T8-. Cytotoxic clones were generated from all MLTCs. Their target cell repertoire (based on an analysis of greater than 30) was generally broad including cell lines sensitive to natural killer (NK) cells, and less frequently and to a weaker extent, fresh autologous and allogeneic tumours. An ovarian carcinoma was exceptional, insofar as the CTX of 8/9 clones was apparently restricted to the autologous tumour. Phenotypically cytotoxic clones were T3+T4-T8+, less usually T3+T4+T8-, but invariably B73.1- (a monoclonal antibody reactive with the peripheral blood NK subset). Analysis at the clonal level emphasises the diversity of responses to putative human tumour-associated antigens, and the need to identify the critical functionally active molecules in the MLTC.

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“…We have previously reported that tumour-associated T cells proliferate vigorously in response to autologous non-T cells in cancer patients with malignant pleural effusions [17]. However, the reactions observed in the autologous MLTC are unlikely to result from auto-recognition of HLA-DR antigens, since neither the proliferative response [30] nor development of auto-tumour cytotoxicity was blocked by monoclonal antibodies against HLA-DR antigens (unpublished observation). Furthermore, positive autologous MLTC reactions were recorded irrespective of the expression of class I and class II major histocompatibility (MHC) antigens on effusion tumour cells (data not shown).…”

Section: Discussionmentioning

confidence: 82%

Lysis of fresh human tumour cells by autologous tumour-associated lymphocytes: Two distinct types of autologous tumour killer cells induced by co-culture with autologous tumour

Uchida

Moore

1985

Cancer Immunol Immunother

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The specific and natural killer (NK)-restricted nature of auto-tumour cytotoxicity of tumour-associated lymphocytes was studied in cancer patients with malignant pleural effusions. Large granular lymphocytes (LGL) and small T lymphocytes were isolated from carcinomatous pleural effusions by centrifugation on discontinuous Percoll gradients. Tumour cells freshly isolated from pleural effusions were classified according to their susceptibility to lysis by Percoll-purified LGL from the blood of normal donors in a 4-h 51Cr release assay. Of 12 NK-sensitive tumour samples, 11 were killed by autologous fresh effusion LGL, whereas only 2 were lysed by autologous T cells. Neither LGL nor T cells were cytotoxic to NK-resistant autologous tumour cells. T cells and LGL were each cultured in vitro with autologous tumour cells for 6 days. Effusion LGL maintained their auto-tumour killing activity in 10 of 12 autologous mixed lymphocyte-tumour cultures (MLTC) with NK-sensitive tumour, while LGL lost the activity when cultured alone. Removal of high-affinity sheep erythrocyte-rosetting cells from Percoll-purified LGL enriched effector cells. Autologous MLTC-derived LGL could also kill NK-sensitive allogeneic effusion tumour cells and K562 cells, as did fresh LGL. In autologous MLTC LGL failed to acquire lytic function to NK-resistant autologous tumour cells. In contrast, in vitro activation of effusion T cells with autologous tumour cells induced auto-tumour killer cells in 9 of 12 NK-sensitive tumour samples and 3 of 6 NK-resistant tumour cases. However, cultured T cells were incapable of killing allogeneic tumour cells and K562 cells. In the autologous MLTC effusion T cells proliferated vigorously in response to autologous tumour cells, whereas LGL showed no proliferation. The enrichment of blasts from cultured T cells on discontinuous Percoll gradients resulted in an enhancement of auto-tumour cytotoxicity, with no reactions recorded in blast-depleted, small, resting T cells. These results indicate that two distinct types of auto-tumour-recognising lymphocytes, LGL and T cells, are present in carcinomatous pleural effusions of cancer patients and that each effector type recognises different membrane moieties of autologous effusion tumour cells.

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DR antigens expressed on tumor cells do not contribute to the blastogenetic response of autologous T cells

Cited by 25 publications

References 23 publications

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

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

Proliferative and cytotoxic responses of human peripheral blood lymphocytes to autologous malignant effusions

Lysis of fresh human tumour cells by autologous tumour-associated lymphocytes: Two distinct types of autologous tumour killer cells induced by co-culture with autologous tumour

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