Activated T lymphocytes within human solid tumors (original) (raw)
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Human tumor-lymphocyte interactionin vitro. III. T lymphocytes in autologous tumor stimulation (ATS)
International Journal of Cancer, 1978
The T-cell nature of the responding cells In autologous tumor stimulation (ATS) was proven by (1) E-rosette formation of lymphocytes attached to tumor cells during the early period of co-cultivation; (2) blast-transformed E-rosetting cells detectable at the end of the test period (day 6) and (3) the reactivity of 1-enriched lymphocyte subset and unresponsiveness of 1-depleted fractions. Preparation of tumor suspensions devoid of lymphocytes made it possible to carry out cross-tests between patients. Blastogenesis with allogenelc tumors was rare. The restricted autologous nature of the reaction is a strong indication for genuine tumor-relatedness.
Human tumor ? Lymphocyte interaction in vitro
Cancer Immunology Immunotherapy, 1978
Biopsy derived tumor cells have been tested for capacity to induce DNA synthesis in autologous blood lymphocytes in vitro (ATS tesO. In the present series 5/20 biopsies were A TS positive when mechanically separated cells were used. Preincubation of the tumor cells at 37 ° C, but not at O°C, markedly increased the stimulating capacity. Parallel experiments gave 7/9 positive tests with preincubated and 3/9 positive tests with cells used directly. When the biopsy cells were brought into suspension by enzyme treatment they did not stimulate unless incubated at 37 ° C before confronting the lymphocytes. In accordance with previous results, the presence of autologous serum during A TS inhibited the reaction.
Cell Adhesiveness Is Related in Malignant Lymphoid Cells to Tumorigenicity
1984
Mouse lymphoma cells ($49) 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 108 cells per mouse. In addition, mice inoculated once with live adherent cells were immunized against 1 x 107 suspension-growing cells. Involvement of an immune response in the rejection of tumorigenic 49cellswassuggestedby(a)adoptivetransferexperimentsinwhichspleencellsfromimmunizedmiceprotectednaivemiceand(b)theappearanceofantibodiesintheseraofimmunizedsyngeneicmicethatspecificallyrecognizedbothadherentandsuspension−growing49 cells was suggested by (a) adoptive transfer experiments in which spleen cells from immunized mice protected naive mice and (b) the appearance of antibodies in the sera of immunized syngeneic mice that specifically recognized both adherent and suspension-growing 49cellswassuggestedby(a)adoptivetransferexperimentsinwhichspleencellsfromimmunizedmiceprotectednaivemiceand(b)theappearanceofantibodiesintheseraofimmunizedsyngeneicmicethatspecificallyrecognizedbothadherentandsuspension−growing49 cells and detected differences in [35S]methioninelabeled antigens from these cells. Antibodies raised in rabbits against adherent cells recognized three proteins of 34,000, 61,000, and 72,000 apparent molecular weight in radiolabeled adherent cell extracts that are either absent or present in small amounts in extracts of suspension-growing tumorigenic $49 cells. These findings, taken together with our previous report (
Effect of tumor cells on the generation of cytotoxic T lymphocytes in vitro
European Journal of Immunology, 1977
Medi-lCenter. Dumam'and lmmunolow Effect of tumor cells on the generation of cytotoxic T lymphocytes in vitro 1. Accessorv cell functions of mouse tumor cells in the Division of Immunology, Duke University generation of cytotoxic T lymphocytes in vitro: replacement of adherent phagocytic cells by tumor cells Branch, National Cancer Institute, National Institutes of Health, Bethesda' or 2-mercaptoethanol* In agreement with previous reports, the primary in vitro response to alloantigens has been shown t o be dependent o n the presence of m a c r e phages (Mphs). Splenocytes extensively depleted of adherent phagocytic cells did not generate cytotoxic T lymphocytes, and this activity could be completely restored by small numbers of adherent peritoneal cells (accessory cells). Either P388D1 (Mph-like tumor), P388 ("null" tumor) or P8 15 (mastocytoma) tumor cells, or 2-mercaptoethanol, could completely replace the accessory function normally mediated by accessory cells. These tumor cells did not nonspecifically "enhance" the cytotoxic activity generated with normal nondepleted spleen cells. The restored cultures maintained killing specificity t o H-2 targets which was mediated by effector T cells as shown by sensitivity t o anti-@ and complement. Therefore, Mphs seem not t o be the sole cells capable of mediating an accessory function in a primary response t o alloantigens in vitro.
Studies of lymphocyte stimulation to tumor-associated antigen
Cancer Immunology Immunotherapy, 1979
Lymphocyte stimulation to 3 M KCl extracts of fresh human tumors was studied by measuring the incorporation of 3H-labeled protein and nucleic acid precursors. L ymphocytes from cancer patients and normal donors were incubated with autologous and allogeneic extracts. Duplicate lymphocyte cultures were labeled with 3H-leucine (3H-Leu), 3H-uridine (aH-Udr), or 3H-thymidine (3H-Tdr). All patients were sensitized to keyhole limpet hemocyanin (KLH) prior to testing. Of the 29 cancer patients tested, many demonstrated significant uptake of 3H-Udr (90%) and 3H-Leu (62%), but not 3H-Tdr (7%) in response to soluble tumor extracts. However, most patients demonstrated uptake of all three precursors in response to KLH. Lymphocytes from cancer patients did not undergo morphologic blast cell transformation in the presence of tumor extracts. Significant incorporation of 3H-Leu and 3H-Udr was seen after 24-48 h of incubation, while significant 3H-Tdr incorporation was not detected until day 5. Stimulation by KLH was significantly greater for all isotope precursors than stimulation in response to tumor extracts. Responses of lymphocytes from normal donors to tumor extracts were noted, although they occurred less frequently than in lymphocytes from cancer patients. L ymphocytes from cancer patients incorporated 3H-Leu and 3H-Udr, but only rarely incorporated 3H-Tdr in response to 3 M KCl extracts of fresh tumors.
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...