Natural and activated cytotoxic lymphocytes which act on autologous and allogeneic tumor cells

Klein, Eva; Vánky, Farkas

doi:10.1007/bf00199488

Cited by 44 publications

(23 citation statements)

References 36 publications

(25 reference statements)

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“…When lysis of fresh human tumor cells was observed, it was present in only a small percentage of the samples tested (8)(9)(10)(11). Recently (12) we reported that peripheral blood leukocytes (PBL) from cancer patients could be activated in culture in preparations of interleukin-2 (IL-2), resulting in the development ofeffector cells cytotoxic for autologous fresh solid tumor cells in short-term 51chromium release assays in >90% of cancer patients tested.…”

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confidence: 99%

“…Such reports include anomolous cytotoxicities, distinct from CTL during alloactivation (13)(14)(15)(16)(17), lectinactivated killing, distinct from lectin-dependent killing (18), fetal calf serum cultureinduced killers (16,(19)(20)(21), and mixed-lymphocyte tumor interaction (MLTI)-induced killers, found only when proliferation was stimulated (8)(9)(10)(11)22). Though fresh tumor targets were rarely used in those studies, our previous reports of lysis of autologous fresh solid tumor cells after allosensitization (23) or lectin activation (24), and those of others after MLTI (8)(9)(10)(11), support this hypothesis and suggest that lymphokine activated killers (LAK) represent a unique and fundamental cytotoxic effector system that may play a role in immune surveillance against NK resistant solid tumor cells, and may have a possible role in the adoptive immunotherapy of tumors.…”

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confidence: 99%

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Lymphokine-activated killer cell phenomenon. Lysis of natural killer-resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes.

Grimm

Mazumder

Zhang

et al. 1982

The Journal of Experimental Medicine

2,000

629

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Activation in lectin-free interleukin 2 (IL-2) containing supernatants of peripheral blood mononuclear leukocytes (PBL) from cancer patients or normal individuals resulted in expression of cytotoxicity toward 20 of 21 natural killer (NK)-resistant fresh solid tumor cells tested. Fresh solid tumor cells were resistant to NK-mediated lysis in 10 autologous patients' PBL-tumor interactions, and from 17 normal individuals tested against 13 allogeneic fresh tumors. Culture of PBL in IL-2 for 2-3 d was required for the lymphokine activated killers (LAK) to be expressed, and lytic activity toward a variety of NK-resistant fresh and cultured tumor targets developed in parallel. Autologous IL-2 was functional in LAK activation, as well as interferon-depleted IL-2 preparations. Irradiation of responder PBL before culture in IL-2 prevented LAK development. Precursors of LAK were present in PBL depleted of adherent cells and in NK-void thoracic duct lymphocytes, suggesting that the precursor is neither a monocyte nor an NK cell. LAK effectors expressed the serologically defined T cell markers of OKT.3, Leu-1, and 4F2, but did not express the monocyte/NK marker OKM-1. Lysis of autologous fresh solid tumors by LAK from cancer patients' PBL was demonstrated in 85% of the patient-fresh tumor combinations. Our data present evidence that the LAK system is a phenomenon distinct from either NK or CTL systems that probably accounts for a large number of reported nonclassical cytotoxicities. The biological role of LAK cells is not yet known, although it is suggested that these cells may be functional in immune surveillance against human solid tumors.

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confidence: 99%

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confidence: 99%

Lymphokine-activated killer cell phenomenon. Lysis of natural killer-resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes.

Grimm

Mazumder

Zhang

et al. 1982

The Journal of Experimental Medicine

2,000

629

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“…For an evaluation of the cytotoxicity of lymphocytes against tumour in cancer patients, studies on autologous combinations of fresh effector and target cells have been performed. Blood lymphocytes from about 25% of cancer patients express lysis of autologous, freshly isolated tumour cells in a short-term assay [1,9,19,29,34]. Our recent studies have shown that lytic potential to autologous fresh tumour cells is present in the peripheral blood and pleural effusions of cancer patients and that it is associated with a minor proportion of large granular lymphocytes (LGL) and is restricted to the cell population that can lyse natural killer (NK)-sensitive K562 cells [15,20].…”

Section: Introductionmentioning

confidence: 99%

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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“…Again lysis was specific for tumor as apposed to nor mal tissues [2], More recently, another form of non specific tumor cytolysis has been demonstrated in vi tro by several groups. This phenomenon has been recently reviewed by Klein and Vanky [3]. Lym phocytes with tumor-lytic potential may be generated in vitro by several types of stimulation.…”

Section: Introductionmentioning

confidence: 99%

Alloantigen-Activated Lysis of Syngenic Tumor Augmented by Allogenic Lymphocytes as Cold Targets

Sugarbaker¹,

Matthews²

1985

Oncology

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In the past, most work in tumor immunology involved attempts to demonstrate tumor-specific transplantation antigens; however, recent in vitro work has shown that it is not necessary to sensitize to a specific tumor antigen to achieve lysis of syngenic tumor cells. Responder spleen cells from B6AF₁ mice (H-2^a_’^b) were sensitized in mixed lymphocyte cultures (MLC) to alloantigens on spleen cells from B10.D2 (H-2^d) mice. In cell-mediated lympholysis (CML) assays the relevant allogenic P815 (H-2^d) tumor targets and B10.D2 lymphoblast targets were lysed. In addition, the semisyngenic tumor target EL-4 (H-2^b) was lysed but RDM-4 (H-2^k) was not. B10.BR (H-2^k), C57BL/6 (H-2^b) and B6AF₁ lymphoblasts were not lysed. If lymphocytes were added as cold targets to the CML assay, B10.D2 lymphocytes completely absorbed lytic activity when B10.D2 lymphoblasts were the target. If B10.D2 lymphocytes were added when P815 was the target, lysis was reduced but could not be abolished. When B10.D2 lymphocytes were added with EL-4 as a target, lysis doubled. These experiments show that the neoplastic determinant on tumor cells recognized by alloantigen-activated lymphocytes does not cross-react with stimulator cell alloantigen and is not an alien histocompatibility antigen. These observations should be considered when in vivo attempts are made to control tumor with in vitro activated lymphocytes; transfer of not only in vitro activated cells but also allogenic stimulator cells to the tumor site may be necessary for maximal tumor destruction.

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Natural and activated cytotoxic lymphocytes which act on autologous and allogeneic tumor cells

Cited by 44 publications

References 36 publications

Lymphokine-activated killer cell phenomenon. Lysis of natural killer-resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes.

Lymphokine-activated killer cell phenomenon. Lysis of natural killer-resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes.

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

Alloantigen-Activated Lysis of Syngenic Tumor Augmented by Allogenic Lymphocytes as Cold Targets

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