concanavalin-a and Carcinoma--Renal-Cell

Interleukin-2 plays a crucial role in enhancing the antitumor immune response. Clinical trials, mainly in renal cell carcinoma and melanoma patients, have been carried out with encouraging results. Recent reports demonstrated that interleukin-2 therapy may depress the immune response either in vitro or in vivo. We decided to monitor, in nine renal cancer patients, the proliferative responses and the parallel variations in Ca2+ homeostasis of peripheral blood lymphocytes collected before, during and after the first cycle of a 3-day interleukin-2 systemic administration. The proliferative response to phytohemagglutinin or concanavalin A significantly dropped early during interleukin-2 infusion. Consistently, an impairment in mobilizing Ca2+, either from internal stores or via influx from outside, was observed. Results obtained with a mAb-alpha CD3 molecular complex strongly suggested that the TCR/CD3 signal transduction pathway was defective. In contrast, no major variations were observed in the general machinery controlling Ca2+ homeostasis nor in the total Ca(2+)-releasable pool. Patients' lymphocytes, cultured in vitro for 3 days in medium alone, showed an almost complete recovery in their ability to respond to mitogens. In conclusion, we show that interleukin-2 administration in cancer patients induces a reversible state of anergy in circulating lymphocytes, assessed both by the reduction in the proliferative response and the block of the mitogen-activated intracellular Ca2+ signalling.

Topics: Calcium; Carcinoma, Renal Cell; Cells, Cultured; Concanavalin A; Homeostasis; Humans; Immunotherapy; Interleukin-2; Ionomycin; Kidney Neoplasms; Lymphocyte Activation; Lymphocytes; Muromonab-CD3; Phytohemagglutinins; Recombinant Proteins; Second Messenger Systems; Signal Transduction; Stimulation, Chemical; Terpenes; Thapsigargin

We investigated the immunomodulatory capacity of primary cultures of renal cell carcinomas (RCC) by assessing production of cytokines and modulation of mitogen-induced T lymphocyte blast transformation. The results clearly show that immunomodulatory capacity is a common feature of RCC and that in vitro these tumors can produce interleukin-10 (IL-10) up to 20 ng/ml, IL-6 up to 35 micrograms/ml (> 250 kU/ml in the B9 system), IL-11 up to 15 micrograms/ml, and transforming growth factor-beta 1 (TGF-beta 1) up to 22 ng/ml. Furthermore, these tumors have the capacity to modulate T cell blast transformation over two orders of magnitude in each direction. The correlations of the immunologic properties of tumor cell cultures with the conventional classification of tumors (histology, cytology, staging, grading, presence of metastases, and secondary tumors) are analyzed. The significance of these findings for modulation of local immunity by RCC as well as for patient outcome is discussed.

Topics: Adjuvants, Immunologic; Carcinoma, Renal Cell; Concanavalin A; Humans; Interleukin-10; Interleukin-11; Interleukin-6; Interleukins; Kidney Neoplasms; Lymphocyte Activation; Mitogens; Reference Values; T-Lymphocytes; Transforming Growth Factor beta; Tumor Cells, Cultured

Long-Evans (Eker) rats carry a mutation that predisposes them to develop spontaneous renal cell tumors of two morphologic patterns: solid chromophilic masses or cystic lesions lined by eosinophilic cells. Previous studies have suggested that these tumors arise from the proximal tubules. In the present study, lectin-binding characteristics and cytokeratin expression of various stages of hereditary rat renal epithelial neoplasia were examined to localize the portion of the nephron from which tumors arise. Lectin-binding histochemistry has been used as a marker of cell surface glycoprotein expression, thought to be important in the differentiation of benign from malignant epithelial lesions and in the determination of their cell of origin. The presence or absence of keratin intermediate filaments in the rat nephron has been used to identify nephron segments. The polyclonal antibody to high- and low-molecular-weight cytokeratin stained the cells of the collecting ducts but not the proximal or distal tubules. Binding to the proximal tubules by the lectins Conavalia ensiformis (Con A), Dolichas biflorus, Ricinus communis (RCA-1), and Triticum vulgare and to the distal tubules by Con A, RCA-1, Arachis hypogaea (PNA) with and without neuraminidase, and the antibody for cytokeratins was demonstrated. The lectin binding and cytokeratin staining patterns of rat hereditary renal cell carcinoma, adenoma and the preneoplastic lesions of atypical tubules and hyperplasias suggest that cystic adenomas arise from the distal nephron, principally the collecting duct, whereas the solid atypical tubules, hyperplasias, and adenomas arise from the proximal nephron, principally the proximal tubule.

Topics: Adenoma; Animals; Biomarkers, Tumor; Carcinoma, Renal Cell; Concanavalin A; Histocytochemistry; Hyperplasia; Immunohistochemistry; Keratins; Kidney Neoplasms; Kidney Tubules, Distal; Kidney Tubules, Proximal; Lectins; Male; Plant Lectins; Precancerous Conditions; Rats; Rodent Diseases; Wheat Germ Agglutinins

Concanavalin A (Con A)-induced suppressor cell activity against the proliferative response of autologous lymphocytes to phytohemagglutinin was examined in peripheral blood lymphocytes derived from 12 normal control subjects and 25 patients with renal cell carcinoma (RCC). The Con A-induced suppressor cell activity in patients with RCC (23.4 +/- 21.4%) was significantly higher than that in control subjects (9.7 +/- 10.7%, P less than 0.05). No significant difference between the degree of suppressor cell activity and stage of disease, grade of malignancy, or cell type was found, although the suppressor activity in patients with tumor microscopically infiltrated by lymphocytes was significantly higher than in patients without lymphocyte-infiltration into the tumor (P less than 0.05). Furthermore, compared with control subjects, Con A-induced suppressor activity in patients with high stage and in those with lymphocyte infiltration into the tumor was significantly higher (P less than 0.05 and P less than 0.01, respectively). In conclusion, because patients with RCC have high suppressor cell activity, abrogation of this activity may be necessary to treat the RCC.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Renal Cell; Concanavalin A; Female; Humans; Kidney Neoplasms; Male; Middle Aged; T-Lymphocytes, Regulatory

The increased serum level of alpha-fetoprotein (AFP) in a case of renal cell carcinoma, a rare condition of AFP production by mesoderm-derived cells, was evaluated for its lectin reactivity by affinity electrophoresis, followed by the antibody-affinity transfer to nitrocellulose membranes for visualization of separated AFP bands. The AFP of this case was characterized by relative increases of concanavalin A-nonreactive AFP-C1 (60.4%), erythroagglutinating phytohemagglutinin-reactive AFP-P4 (37.8%) and AFP-P5 (46.3%) and Allomyrina dichotoma lectin-nonreactive AFP-A1s (66.7%), and by the total absence of lentil lectin-reactive components, AFP-L2 and AFP-L3. Thus, the lectin-reactive pattern of AFP markedly deviated not only from that of cord serum, but also from those of other malignancies and of fetal kidney cells in culture.

Topics: alpha-Fetoproteins; Carcinoma, Renal Cell; Concanavalin A; Electrophoresis, Agar Gel; Humans; Lectins; Male; Middle Aged; Phytohemagglutinins

The effect of lectins on cultured renal cell carcinoma and normal renal cells was studied. Ricin II showed effective inhibition of 3H-uridine and 3H-thymidine uptake by renal cell carcinoma and normal renal cells in all cases. Normal renal cells were more resistant to the inhibitory effect of ricin II as compared to renal cell carcinoma. Concanavalin agglutinin and wheat germ agglutinin led to stimulation of 3H-uridine and 3H-thymidine uptake by renal cell carcinoma and normal renal cells at low concentrations (0.2 micrograms/ml), and to suppression at high concentrations (2 and 20 micrograms/ml).

Topics: Carcinoma, Renal Cell; Cells, Cultured; Concanavalin A; Humans; In Vitro Techniques; Kidney; Kidney Neoplasms; Kinetics; Lectins; Plant Lectins; Thymidine; Uridine; Wheat Germ Agglutinins