PubMed Health⌕ Search

Biomedical subjects

B M Vose

Publications and source records attributed to B M Vose.

At least 37 records · Page 2Linked to original sources
PubMed1981

Extravascular natural cytotoxicity in man: Anti-K562 activity of lymph-node and tumour-infiltrating lymphocytes.

A major distinction is reported between the cytolytic activity of peripheral blood lymphocytes (PBL) and that of lymph-node and tumour-infiltrating lymphocytes (TIL) against targets of the NK-sensitive K562 cell line in short-term 51Cr release assays. In the PBL of normal donors and lung cancer patients in whom disease was advanced anti-K562 reactivity, though variable, was consistently detectable and this activity could be augmented to a similar extent in patients and controls by treatment of effectors with exogenous interferon (IF). By contrast anti-K562 activity in lymph-node cells (LNC) and TIL was virtually absent and significant levels could not be induced by exposure to IF. This activity was not attributable to coexistent suppressor cells for NK function since admixture of LNC and TIL with normal PBL failed to modulate K562 killing by the latter. The results imply that K562-reactive NK cells and their precursors may frequently be present at sub-threshold levels in the lymph nodes of tumour-bearing patients and a similar explanation could account for the inactivity of TIL. However, in the latter situation, actively-induced NK dysfunction in situ incapable of regeneration by IF, and attributable to as yet undefined tumour-associated factors, may also be involved.

Animals↗
PubMed1981

Cultured human T-cell lines kill autologous solid tumours.

Lymphocytes from peripheral blood, lymph node, spleen and tumour of 7 patients with various carcinomas (2 lung, 3 colon, 1 gastric and 1 parotid tumour) were cultured for 15 days in conditioned media containing T-cell growth factor (TCGF; Interleukin 2) after which their cytotoxic activity against autologous tumour (and in some instances, autologous normal) cells and allogeneic tumour targets was evaluated in a short-term 51Cr-release assay. Significant cytotoxicity against autologous tumour targets was detected in at least one effector preparation from all of the patients, under conditions where, in some cases, other autologous cells (normal lung, PHA-transformed lymphocytes) were resistant. This cytotoxicity also generally extended to allogeneic tumour targets, but lysis of K562, a cell line sensitive to natural killing, occurred in only 3 of 19 effector cell preparations. The data are consistent with a polyclonal expansion of cytotoxic T-cells of tumour-bearing patients which includes the amplification of a population recognitive of antigens expressed on autologous neoplastic cells.

Cell Line↗
PubMed1981

Specific and non-specific lymphocyte cytotoxicity in colon carcinoma.

The cytotoxic activity of peripheral-blood (PBL), lymph-node (LNC) and tumour-infiltrating lymphocytes (TIL) from 47 patients undergoing surgery for colon carcinoma (Duke's Stage A, 1 patient; B, 24; C, 15 and C with metastases, 7) was examined in short-term 51Cr-release assays, against fresh autologous tumour cells, allogeneic colon cancer cells and the erythroleukaemia cell line, K562. Cytotoxicity against autologous cells was detected in at least one effector population in 23/47 patients (49%), with overall frequencies which did not differ for patients in different Duke's stages of disease. By contrast, lysis of allogeneic tumour cells was infrequent (11%) regardless of the effector population to which they were exposed. Cytotoxicity against K562, cells highly sensitive to NK activity, though variable, was detected in 93% of PBL of normal donors and 83% of patients, and among the latter showed no evidence of significant decline with advancing disease. However, LNC and TIL anti-K562 activity was infrequent (17%) in concordance with previous reports. There was no correlation between the ability of patients' PBL to lyse autologous tumour and K562 cells. The independence of these 2 cytotoxic actions was further explored in studies fractionating lymphocytes: autologous tumour killing was augmented in T-enriched PBL; whereas the greatest anti-K562 activity was found in the corresponding non-T fraction. Lymphocyte cytotoxicity in colonic neoplasia is thus manifest in 2 apparently independent lymphocyte populations; a relatively specific killer T-cell population, detectable in PBL, LNC and TIL, which is preferentially reactive with the autologous cells; and a non-specific killer population, largely limited to PBL, with the properties of NK cells. The activity of neither population reflects the clinical status of patients with this disease.

Adult↗
PubMed1981

Expansion of autorecognitive cytotoxic effectors in human cancer by T cell growth factor (Interleukin 2)1.

Conditions for the production of supernates from mitogen stimulated human lymphocytes with the capacity to induce proliferation in long term MLC or PHA stimulated cultures which no longer respond to PHA have been investigated. These supernates can be used to maintain lymphocytes in continuous growth with a doubling time of approximately 48 hours. Cells grown from MLC stimulated cultures show less than 80% SRBC rosetting cells, are Fc-, do not show ADCC activity and induce reduced lysis of K562 compared with freshly isolated effectors. Cultured T cells (CTC) show high lytic activity against the inducing PHA blasts but not autologous or third part targets. Similar experiments have been performed with lymphocytes from the blood, lymph node, spleen and tumour of cancer patients and CTC tested for cytotoxicity against autologous and allogeneic tumour cells and the K562 compared with freshly isolated effectors. Cultured T cells (CTC) show high lytic activity against the inducing PHA blasts but not autologous or third part targets. Similar experiments have been performed with lymphocytes from the blood, lymph node, spleen and tumour of cancer patients and CTC tested for cytotoxicity against autologous and allogeneic tumour cells and the K562 cell line. Cytotoxicity for autologous tumour was found in all samples. This was accompanied by killing of allogeneic cells in most instances but killing of K562 was only rarely demonstrable. These data would be consistent with a polyclonal expansion of cytotoxic effectors in the samples. The finding of autologous reactivity suggests the presence of autorecognitive cytotoxic T cells in cancer patients with specificity for tumour. Cloning experiments are currently in progress to investigate this possibility further.

Cytotoxicity, Immunologic↗
PubMed1980

Natural cytotoxicity in humans: susceptibility of freshly isolatd tumor cells to lysis.

The cytotoxic potential of blood lymphocyters from healthy donors was tested against freshly isolated lung cancer cells and the erythroleukemia K562 cell line in short-term 51Cr release assays conducted at an effector:target ratio of 50:1. Most donors exhibited significant activity against K6-562 cells. By contrast, fresh tumor cells were refractory, only 6 of 30 showing significant cytotoxicity. The low susceptibility of these tumor cells was confirmed in third-party cold inhibition assays in which they interfered minimally with killing of K562 targets under conditions in which unlabeled K562 cells efficiently blocked cytotoxicity. Cells prepared from normal lung tissue and Raji cells also failed to inhibit killing. Although in comparison to the K562 cell line freshly isolated tumor cells were resistant, their susceptibility may not be so low as to be biologically irrelevant, inasmuch as boosting of natural killing activity by interferon induced levels of cytotoxicity against both types of target cell that were unattainable by unstimulated effectors. Interferon-boosted killers were lytic for "normal" lung cells and the Raji cell line.

Cell Line↗
PubMed1979

Human tumor-lymphocyte interaction in vitro. VI. Specificity of primary and secondary autologous lymphocyte-mediated cytotoxicity.

A T-cell-enriched lymphocyte subset of samples from 15 tumor patients was tested for primary cytotoxicity against autologous tumor cell preparations and against 1-3 different allogeneic tumor cell preparations from biopsy material. Allogeneic cytotoxicity occurred in only 1 of 10 patients with autologous reactivity. The lymphocytes of 14 patients were cultured with autologous cells from biopsy material for 6 days. These lymphocytes killed autologous targets, but only 1 patient's lymphocytes were cytotoxic against 1 of the 4 allogeneic tumors tested. Cocultivation with allogeneic cells from biopsy specimens generated cytotoxicity toward the sensitizing allogeneic cells in 3 of 9 test combinations. In 2 of 3 instances the effectors were also active against the autologous tumor cells. Cytotoxicity in primary and secondary tests occurred thus only rarely against allogeneic targets. This indicated either the presence of individual tumor-related antigens on the cells from biopsy material or reflected the histocompatibility restriction of T-cell-mediated cytotoxicity.

Antigens, Neoplasm↗
PubMed1978

In vitro generation of cytotoxicity against autologous human tumour biopsy cells.

Blood lymphocytes from 22 cancer patients were examined for cytotoxicity against autologous tumour cells in a short-term 51Cr release assay. Only three showed reactivity. In an attempt to increase cytotoxic potential in these and induce reactivity in non-reactive cases, the lymphocytes were cultured alone or with autologous tumour cells for 6 days. Upon subsequent testing against frozen, stored targets, nine samples reacted, including two of those with primary reactivity. In seven cases augmented cytotoxicity was evident in mixed cultures compared with lymphocytes cultured alone. Two of 10 cases showed cytotoxicity against the K562 cell line after culture and, in two of 13 tests in which allogeneic tumour biopsy targets were used, weak reactivity was bound. Cytotoxicity for autologous tumour biopsy cells was uniformly accompanied by positive blastogenesis in MLTI assays. In four cases blastogenesis occurred without the induction of cytotoxicity.

Cell Line↗
PubMed1978

Restricted autologous lymphocytotoxicity in lung neoplasia.

Blood lymphocytes from 47 patients with lung carcinoma have been tested for cytotoxicity against cells isolated from the autologous tumour. Significant cytotoxic potential was found in 15 cases. The effectors were also tested against allogeneic tumour targets from lung and other sites. Reactions were only rarely detected (2/32 positive against lung and 1/13 positive against non-lung cells). The restriction of cytotoxicity to the autologous combination was also apparent in in vitro-generated effectors. Blood lymphocytes were co-cultivated with autologous tumour and subsequently tested against autologous or allogeneic targets. Cytotoxicity was found in 13/17 lung tumours against autologous tumour, with no reactions recorded against allogeneic tumour targets, but one case positive against the K562 cell line. These data suggest either the expression of individually distinct antigens on human pulmonary neoplasms, or the requirement for histocompatibility between target and effector in cytotoxicity reactions in man, and therefore differ from previously described patterns of lymphocytotoxicity against human tumours.

Cell Line↗
PubMed1977

Human tumour--lymphocyte interaction in vitro. V. Comparison of the reactivity of tumour-infiltrating, blood and lymph-node lymphocytes with autologous tumour cells.

Lymphocytes prepared from the blood, tumour-draining lymph node and tumour were tested for immune reactivity with freshly isolated autologous tumour cells from biopsies. Reactivity was assessed by the autologous tumour stimulation assay and by lymphocytotoxicity. Activity was found in 6/11 blood preparations, 7/10 lymph nodes and 1/7 tumour-infiltrating lymphocytes in tumour stimulation assays and in 6/19 blood, 8/18 lymph-node and 5/20 tumour-infiltrating lymphocytes in cytotoxicity assays. Tests with material from patients with nasopharyngeal carcinoma showed a higher frequency of cytotoxicity in the tumour-infiltrating lymphocytes than in other solid tumours. There was a correlation between results of the two assays when performed on the same preparations and between the levels of reactivity in lymph node and blood from the same patient. Cytotoxicity in the lymph nodes showed specificity in that cells from a long-term culture (K562) known to be sensitive to natural killer activity and from allogeneic tumour biopsies were only rarely damaged. Cytotoxicity against K562 was more frequently determined in blood lymphocytes. Tumour-infiltrating lymphocytes were non-reactive in patients when the blood and lymph-node lymphocytes were active.

Cytotoxicity, Immunologic↗
PubMed1977

Lymphocyte cytotoxicity against autologous tumour biopsy cells in humans.

By the application of separation techniques in a stepwise manner to mechanically prepared cell suspensions from human tumour biopsies it has been possible to isolate tumour cells having high viability and low contamination with host cells. These tumour cells have been used as targets in 51Cr release cytotoxicity assays using autologous lymphocytes from blood or lymph node as effectors. It has been possible to investigate this reactivity in 30 patients with malignant and four patients with benign tumours. Significant autologous cytotoxicity in the blood lymphocytes was detectable in two of 12 lung tumours, nine of 18 other carcinomas and sarcomas but in none of the benign cases. Cytotoxicity was not limited by the presence of obvious residual disease at the time of operation although reactivity was less frequently detectable in patients with secondary involvement. Reactivity in the tumour-draining lymph nodes largely paralleled that in the blood in the limited number of patients examined. The technical problems encountered during this study and the role of natural cytotoxicity in the interpretation of these data are discussed.

Animals↗
PubMed1977

Natural cytotoxicity in man: activity of lymph node and tumor-infiltrating lymphocytes.

Lymphocytes from blood, lymph node and tumor have been tested for cytotoxicity against the K562 cell line which is known to be highly sensitive to lysis by spontaneously reactive cells. Cytotoxicity was found in all 13 samples from healthy donors and in 17/32 cancer patients. By contrast, activity was determined in only 1/18 lymph node and 1/14 preparations of tumor-infiltrating lymphocytes. Lymph node cells were similarly nonreactive against 3 other cell lines known to be sensitive to natural cytotoxicity. Studies of the composition of the effector populations revealed no absolute deficit of a particular cell type although there were differences between them resulting from the different isolation procedures used. Enrichment of the lymph node population for non-T, non-B lymphocyte was ineffective in inducing cytotoxicity in previously nonreactive samples although this procedure uniformly increased the cytotoxic potential of blood lymphocytes. Tests with blood taken during operation showed that the lack of reactivity in these preparations was unlikely to be a result of the effects of anesthesia or surgery. The reason for the low cytotoxicity in the lymph node and tumor-infiltrating lymphocytes is as yet undefined.

Anesthesia↗
PubMed1977

Reactivity of peripheral blood leukocytes against human foetal cells. II. Cytotoxic potential of preparations enriched or depleted of different leukocyte populations.

Leukocytes separated initially by Ficoll-Triosil sedimentation from the peripheral blood of 62 healthy donors and 64 patients with a variety of cancers were tested for cytotoxicity against cells from a single human foetal lung, by means of a microplate technique based on visual enumeration of surviving target cells. Under these conditions cytotoxicity was primarily observed to be a function of the granulocyte content of the preparations, which was extremely variable (range 0-60%). When the influence of these cells was greatly diminished through depletion by adherence, residual cytotoxicity was still detectable in the majority of samples tested. Complete abrogation of this cytotoxicity by pretreatment with carrageenan implicated cells of the monocyte-macrophage series, which persisted as a small minority (about 2%) in the already depleted effector cell populations. However some cytotoxicity could also be demonstrated in populations, purified by passage through columns containing nylon fibre or Degalan-coated (human Ig-anti Ig) beads, which consisted almost exclusively (about 98%) of lymphocytes, mainly of thymus (T)-dependent type (greater than or equal to 80%). Under these conditions and those in which T-cells were concentrated by formation of spontaneous E rosettes, cytotoxicity appeared to decline with T cell enrichment, suggesting that the cytolytic effects were attributable to cells of the non T-compartment which were present to a variable extent in the different T-cell-enriched populations. Although the absolute identity of these cells was not established, the experiments illustrate potential sources of non-specific cytotoxicity among different effector cell populations against target cells expressing antigens to which the majority of leukocyte donors--in health or disease--were presumably non-sensitized. As such these data have several implications for the interpretation of in vitro cytotoxicity tests against human neoplasms.

Carrageenan↗