title: Immune inhibitory effects of renal cell carcinoma extract on lectin and alloantigen-induced peripheral blood and tumor infiltrating lymphocyte blastogenesis.
abstract: The presence of tumor infiltrating lymphocytes (TIL) has been attributed to the host cell mediated immune response against the evolving malignancy. However, due to specific evasive and escape mechanisms, the immune competent cells are rendered ineffective. One such mechanism may be the production of immune suppressor substance(s), inhibiting lymphocyte proliferation, and subsequently, their transformation into effector cells. To evaluate a possible impact of RCC extract on lectin and alloantigen-induced proliferation of TIL and peripheral blood lymphocytes (PBL) from renal cell carcinoma (RCC) patients and from healthy control human subjects. Tumor extract and TIL were derived from 13 patients with RCC undergoing radical nephrectomy. Tumor infiltrating lymphocytes and PBL from these patients were activated with Concanavalin A (Con-A), Phytohemoglutinine (PHA) or Pokeweed (PW) and the rate of blastogenesis was measured by (3)H Thymidine incorporation. The same procedure was used in assay with PBL from control healthy blood donors. There was a significant reduction (88.6%) in the proliferative response to ConA of TIL compared to PBL from the same patients (P = 0.007). A similar decrease was seen following stimulation by PHA (85.8%, P = 0.01) and PW mitogen (78.5%, P = 0.001). A 79.5% decrease in response level of TIL to alloantigens compared to PBL from RCC patients (P = 0.021), was observed. Lectin induced proliferative response of RCC patients was significantly lower in the presence of RCC extract (82.9%) compared to normal kidney extract (P = 0.008). Alloantigenic stimulation of healthy individual PBL was also decreased significantly in the presence of RCC extract (92.9%, P = 0.0001) compared to normal kidney extract. Similarly, lectin induced stimulation of healthy control PBL in the presence of RCC extract was significantly lower (83.2%, P = 0.003). Our data suggest that RCC extract contains an immune suppressive substance(s), capable of inhibiting lymphocyte proliferative response of tumor infiltrating lymphocytes as well as of PBL from patients and healthy individuals alike. This may be one of the mechanisms by which the tumor evades the transformation of lymphocytes into effector killer cells, and thus affects the biological inter-relationship between tumor and host. Identification of this substance and its gene may provide an effective anti-tumoral treatment modality.
authors.affiliation: The Transplantation Service and the Department of Urology, State University of New York at Stony Brook, Stony Brook, New York 11794, USA.
authors.forename: M
authors.initials: M
authors.lastname: Shabtai
authors.forename: H
authors.initials: H
authors.lastname: Ye
authors.forename: K
authors.initials: K
authors.lastname: Kono
authors.forename: T
authors.initials: T
authors.lastname: Takayam
authors.forename: K
authors.initials: K
authors.lastname: Terashima
authors.forename: K
authors.initials: K
authors.lastname: Tsukuda
authors.forename: Z
authors.initials: Z
authors.lastname: Frischer
authors.forename: W C
authors.initials: WC
authors.lastname: Waltzer
authors.forename: K
authors.initials: K
authors.lastname: Malinowski
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000737:chemistry* / Q000276:immunology; D000368:Aged; D001685:Biological Factors / Q000302:isolation & purification / Q000494:pharmacology; D001773:Blood Cells / Q000187:drug effects; D002292:Carcinoma, Renal Cell / Q000737:chemistry* / Q000276:immunology; D002295:Carcinoma, Transitional Cell / Q000737:chemistry / Q000276:immunology; D002478:Cells, Cultured / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007519:Isoantigens / Q000276:immunology*; D007668:Kidney / Q000737:chemistry; D007680:Kidney Neoplasms / Q000737:chemistry* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009928:Organ Specificity; D010835:Phytohemagglutinins / Q000494:pharmacology*; D011043:Pokeweed Mitogens / Q000494:pharmacology*; D014020:Tissue Extracts / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D001685:Biological Factors; D007519:Isoantigens; D010835:Phytohemagglutinins; D011043:Pokeweed Mitogens; D014020:Tissue Extracts; D003208:Concanavalin A