Inhibition of normal allogeneic lymphocyte mitogenesis by a factor released from human tumor cells in culture

Renk, Clifford M.; Gupta, Rishab K.; Morton, Donald L.

doi:10.1007/bf00205768

Cited by 8 publications

(4 citation statements)

References 28 publications

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“…Renk et al [10] demonstrated that supernatants from melanoma, colon, lung, and breast tumour cell lines and normal fibroblast cultures were inhibitory for PHA-induced blastogenesis, but only one colon line and the breast carcinoma cell lines inhibited both PHAand Con A-induced blastogenesis to a significant degree. An inhibitor of spontaneous cell division and PHA responses of normal lymphocytes has also been detected in various established cell lines, including melanoma, bladder carcinoma, the Chang liver cell lines [14], and colonic adenocarcinoma [15].…”

Section: Discussionmentioning

confidence: 97%

Supernatant derived from a human hepatocellular carcinoma cell line (PLC/PRF/5) activates a population of T-suppressor cells

Keong

Rabson

1983

Cancer Immunol Immunother

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Section: Discussionmentioning

confidence: 97%

Supernatant derived from a human hepatocellular carcinoma cell line (PLC/PRF/5) activates a population of T-suppressor cells

Keong

Rabson

1983

Cancer Immunol Immunother

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“…Tumor cells may not only locally produce or induce the formation of soluble immunosuppressive factors [3,4], but they may also in their late growth induce the produc tion of suppressor T cells that are capable of inhibiting the production of cytotoxic T lymphocytes [5]. This can sig nificantly suppress the host's antitumor immune response and remains the major obstacle of successful anticancer immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…How ever as a tumor progressively grows, it may induce deteri oration of the host's antitumor immune response [1,2] by secreting soluble immunosuppressive factors locally [3,4] and inducing the production of suppressor T cells systemically [5], Theoretically, treatments that either eliminate the tumor-induced immunosuppression or augment the host's tumor-specific immune response may be applied either singly or in combination as the armature for anti cancer therapy. Cyclophosphamide (CYC) has been…”

Section: Introductionmentioning

confidence: 99%

Effects of Chemoimmunotherapy with and without Surgery in Murine MBT-2 Bladder Tumor

Tzai¹,

Lin²,

Chow

1994

Urol Int

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Using C3H/He JCr mice bearing the syngeneic MBT-2 bladder tumor, it was found that cyclophosphamide (CYC 100 mg/kg i.p.) treatment, 1 day before and 2 weeks after surgery, followed by postoperative autologous tumor vaccine immunization can be an effective adjuvant anticancer therapy. The short-term exogeneous addition of low dose 11-2 administration to the protocol provided no further benefit. Suppression of tumor growth was observed in a classical Winn assay when splenocytes were obtained on day 23 from mice receiving this effective adjuvant therapy with surgery on day 8. Splenocytes from tumor-bearing mice (TBM) treated with CYC were augmented in terms of their proliferative response to concanavalin A during the first 2 weeks after CYC treatment. Studies using 3-day TBM established that significant suppression of tumor growth and prolonged survivals were dependent upon CYC treatment being combined with tumor vaccine and/or interleukin-2; single agent treatments were ineffective.

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“…Various human and murine tumor-derived factors suppress immune function in vitro as assessed by a variety of techniques Abbreviations: ACK, ammonium chloride-potassium erythrocyte lysing buffer; BSA, bovine serum albumin; CM, complete medium; Con A, concanavalin A; HBSS, Hank's balanced salt solution; HPLC, high-performance liquid chromatography; HS, hepes sucrose; IL-2, interleukin II (lectin-free); IRF, immunoregulatory factor; Leu, L-leueine; LPS, lipopolysaccharide; M3, metastasis from murine melanoma K-1735; MASH, multiple automated sample harvester; PBS, phosphate-buffered saline; PIEF, preparative isoelectric focusing; PHA, phytohemaglutinin; PWM, pokeweed mitogen; Tdr, thymidine Offprint requests to: J. A. Roth [3,4,7,[12][13][14][18][19][20][21][22], yet no study has correlated in vitro and in vivo effects. Human tumor-associated factors inhibit numerous immunological tests in vitro, including mitogen-stimulated blastogenesis, mixed lymphocyte responses, immunoglobulin sytnthesis, proliferation of I1-2-dependent cell lines, accessory function of mononuclear cells, and cell-mediated cytotoxicity [15,16].…”

Section: Introductionmentioning

confidence: 99%

Identification and characterization of a tumor-derived immunosuppressive glycoprotein from murine melanoma K-1735

Putnam

Roth

1985

Cancer Immunol Immunother

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A suppressive immunoregulatory factor (IRF) produced by murine melanoma K-1735 M3 has been identified. Extracts from tissue or cultured cells grown in serum-medium were prepared by 3 M KCl extraction and partially purified by low-salt precipitation. IRF extracted from fresh tumor, cultured cells, and spent medium from the K-1735 cell line suppressed 3H-thymidine incorporation by splenocytes during mitogen stimulation. Cell viability was not impaired by IRF. IRF suppressed splenocyte proliferation, protein synthesis, murine IL-2-mediated blastogenesis, and mixed splenocyte responses. However, in vitro generation of allogenic cytotoxic cells was not suppressed. Significant inhibitory activity could not be extracted from normal tissues. IRF activity was reduced by treatment with proteolytic enzymes and neuraminidase and was bound by lentil lectin, indicating that the factor is a glycoprotein. IRF was heat-stable, yet labile to treatment with acid, base, or 2-mercaptoethanol. Inhibitory activity was partially characterized by preparative isoelectric focusing (pI 3.5-5.8), and the active moiety had a molecular size of 10-12 K according to HPLC. The HPLC-purified active fraction of IRF did not contain the immunosuppressive retroviral antigen p15(E). Splenocytes from animals treated with IRF in vivo demonstrated reduced responses to Con A and PHA in vitro. Suppressor cells were not identified. We have identified a low-molecular-weight glycoprotein from a murine melanoma, which suppresses a variety of immunologic responses in vitro and in vivo. IRF appears to be a potent mediator of tumor-induced immunosuppression in this model.

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Inhibition of normal allogeneic lymphocyte mitogenesis by a factor released from human tumor cells in culture

Cited by 8 publications

References 28 publications

Supernatant derived from a human hepatocellular carcinoma cell line (PLC/PRF/5) activates a population of T-suppressor cells

Supernatant derived from a human hepatocellular carcinoma cell line (PLC/PRF/5) activates a population of T-suppressor cells

Effects of Chemoimmunotherapy with and without Surgery in Murine MBT-2 Bladder Tumor

Identification and characterization of a tumor-derived immunosuppressive glycoprotein from murine melanoma K-1735

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