Activated T lymphocytes within human solid tumors (original) (raw)
International Journal of Cancer, 1976
Spleens from BALB/c mice transplanted with mammary tumors display a significant increase in the percentage of lymphocytes bearing complement receptors (CRL) while the percentage of cells bearing surface immunoglobulins (SIg) remains unchanged in comparison with that in spleens from normal animals. Upon separation on nylon columns, the increase in CRL in the spleens from tumor-bearing mice was limited to the non-adherent cell population. Simultaneous marker analysis disclosed that these CRL lacked detectable SIg. Indirect immunofluorescence indicated that these cells possessed theta antigen. Absence of SIg and the presence of theta antigen coupled with the restricted occurrence of these cells in the nylon-non-adherent population which responded to PHA and Con A but not to LPS indicate that these cells may constitute a subset of T cells. The paucity of this subpopulation of spleen lymphocytes in normal spleen suggests that their emergence is related to tumor growth.Apparition D'une Sous-Population De Lymphocytes Portant L'antigène θ Et Les Récepteurs Du Complément Pendant La Croissance TumoraleDans la rate de souris BALB/c porteuses de tumeurs mammaires transplantées, on a constaté une augmentation significative du pourcentage de lymphocytes portant des récepteurs pour le complément (CRL), tandis que le pourcentage de cellules portant des immunoglobulines à leur surface (SIg) restait inchangé par comparaison avec la rate des animaux normaux. Lors de la séparation sur des colonnes de nylon, on a constaté que l'augmentation des CRL spléniques des souris porteuses de tumeurs ne se produit que dans la population de cellules non adhérentes. Une analyse simultanée des marqueurs a révélé que ces CRL ne portent apparemment pas de SIg. L'immunofluorescence indirecte a indiqué que ces cellules possèdent l'antigène theta. L'absence de SIg et la présence de l'antigène theta, associées au fait que ces cellules n'apparaissent que dans la population non adhérente au nylon qui réagit à la PHA et à la Con A mais pas au LPS, indiquent qu'il s'agit peut-ětre d'une sous-population de cellules T. La rareté de ces lymphocytes spleéniques dans la rate normale conduit à penser que leur apparition est liée à la croissance tumorale.
Cell adhesiveness is related to tumorigenicity in malignant lymphoid cells
Journal of Cell Biology, 1984
Mouse lymphoma cells (S49) that grow in suspension culture were selected for increased tumorigenicity through continuous passages in syngeneic BALB/c mice. Developing tumors were classified as high grade malignant lymphoma, small noncleaved type. Variants were selected from these tumorigenic cells that were able to grow as a monolayer attached to their substrate, resembling, in this respect, fibroblastoid cells. Whereas the tumorigenic suspension-growing parental cells were able to induce progressive tumors with an inoculum as low as 100 cells per mouse, the adherent cells were unable to develop as tumors even at an inoculum of 1 X 10(8) cells per mouse. In addition, mice inoculated once with live adherent cells were immunized against 1 X 10(7) suspension-growing cells. Involvement of an immune response in the rejection of tumorigenic S49 cells was suggested by (a) adoptive transfer experiments in which spleen cells from immunized mice protected naive mice and (b) the appearance of ...
Adherent cells in tumor immunity
Cellular Immunology, 1977
The present studies explored the role of adherent cells in tumor immunity. Lymph node cells from mice bearing large tumors appeared to be maximally stimulated ifi viva and incapable of further stimulation by cells of the same tumor in vitro. Removal of the adherent cell population resulted in a marked decrease in the spontaneous background activity of the remaining nonadherent cells and allowed these cells to undergo stimulation when cultured in the presence of mitomycin-blocked tumor cells. The role of the adherent cell in the maintenance of a state of continuous stimulation was further elucidated by experiments in which lymph node cell populations were reconstituted from the adherent and nonadherent subpopulations. It was also shown that adherent lymphoid cells from tumor-bearing mice, but not from normal mice, were capable of stimulating tumor-immune lymphocytes in a manner similar to intact mitomycinblocked tumor cells.
Stimulation of thymus- and bone marrow-derived lymphocytes by tumor cells in culture
Cancer research, 1977
In vitro lymphocyte stimulation by mitomycin-blocked tumor cells can be used to measure tumor-specific immune responses. In order to determine the responding cell type(s) in this reaction, lymph node and spleen cell populations were specifically depleted of thymus- or bone marrow-derived cells by the use of the appropriate antisera and complement or by immunoadsorption of the Fc receptor-bearing cells to antibody-coated sheep red blood cell monolayers. The compositions of both the original and the modified lymphocyte populations were determined by (a) viability counting following treatment with antisera and complement, (b) direct and indirect immunofluorescence, (c) antibody-coated erythrocyte rosette formation, and (d) response to thymus- and bone marrow-derived cell mitogens. In the lymph node cell populations, only the thymus-derived cells were stimulated by the tumor cells. However, both bone marrow- and thymus-derived cells from tumor-immune spleens underwent stimulation when e...
Journal of Experimental Medicine, 1982
A proportion of patients with carcinomas and sarcomas possess blood lymphocytes that can lyse their freshly harvested tumor cells in vitro (I-4). To enhance such cytotoxicity, we activated the lymphocytes either in mixed cultures with autologous tumor biopsy cells (ATS) 1 or in conventional mixed lymphocyte cultures (MLC). In accordance with the results of Zarling et al. (5), with leukemia cells, MLC-activated lymphocytes were often cytotoxic for autologous and third-party allogeneic solid tumor cells (6). Cocultivation with the patients' tumors generated autotumor cytotoxicity in the majority of experiments (7-9). In contrast to the MLC, these lymphocytes did not lyse allogeneic tumor biopsy cells. The effects against autologous and third-party tumors by the patients' MLClymphocytes might be a consequence of activation of lymphocyte sets that recognize (a) antigens that cross-react with the stimulator lymphocytes (b) tumor-related antigens shared by tumor cells of the lymphocyte donor and the allogeneic tumor, and (c) distinct allo-and/or tumor-related antigens on the different targets. Cold target competition experiments presented in this paper suggest that the third alternative is valid. Establishment of growing T cell lines with maintained specific functions (cytotoxicity or proliferative capacity) is an important step in the progress of tumor immunology (10-17). Such T cell populations reacting with autologous tumor cells might help in the study of the cell surface antigens of tumor cells, and they may be exploited in therapeutical measures. Because T cell growth factor (TCGF) (interleukin 2; IL-2) promotes the growth of activated T cells (18), its use imposes a selection for propagation of specific clones when applied to populations preexposed to the relevant antigen. To raise specific autotumor killer T cell cultures from patients with solid tumors, we cultured the blood lymphocytes first with the autologous tumor cells and thereafter added TCGF to
Cellular Immunology, 1992
Antigen-specific T-cell factors (TCF) play a role in the initiation of cellular immune responses. In allogeneic mouse-tumor models lymphocytes from the direct tumor surroundings of both euthymic and nude mice produce TCF. These lymphocytes produce TCF when collected already 1 day after subcutaneous (sc) injection of tumor cells. In contrast to euthymic mice, draining lymph nodes and spleen of nude mice did not contain TCF-producing lymphocytes at any stage after sc tumor cell injection. In sensitized euthymic mice TCF production by lymphocytes is significantly higher in the direct tumor surroundings than in draining lymph nodes or spleen. At 2 and 5 days after tumor cell injection, the mononuclear cell infiltrate of the tissue surrounding the tumor in euthymic mice showed low expression of Thy 1, CD3, TCR alpha beta, TCR gamma delta, CD4, CD8, and asialo GM1, whereas several lymphocytes and mast cells were positive for monoclonal antibody (mAb) 14-30 (directed against TCF). In both euthymic and nude mice, sc injected tumor cells showed apoptosis. In conclusion, the direct tumor surroundings are the first (and, for nude mice, the only) site of TCF production, sc injection of tumor cells attracts mAb 14-30-positive lymphocytes and renders mast cells positive for mAb 14-30.
Nonspecific suppression of T lymphocyte responses in mice carrying progressively growing tumors
European Journal of Immunology, 1974
Unfractionated spleen cells from mice with four different types of progressively growing tumors were unable t o show enhanced DNA or protein synthesis upon stimulation with phytohemagglutinin (PHA) in vitro. After separation by velocity sedimentation, o r passage over an anti-immunoglobulin column, cells were obtained which could respond t o this mitdgen. An auxiliary population of cells obtained by velocity sedimentation, sedimenting with the characteristics of activated B lymphocytes and sensitive t o the cytotoxic effects of anti-immunoglobulin serum and complement, could depress the response of normal spleen cells challenged with PHA. A role for this cell type in the tumor progression seen in the host animals is discussed.