The Flip Side of Tumor Immunity

Prehn, Richmond T.; Prehn, Liisa M.

doi:10.1001/archsurg.1989.01410010112022

Cited by 18 publications

(9 citation statements)

References 41 publications

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“…this factor, for example by anti-inflammatory therapy (54) or deficiency in homing molecules (e.g., P-selectin [55]), can engender tumor growth attenuation. this factor, for example by anti-inflammatory therapy (54) or deficiency in homing molecules (e.g., P-selectin [55]), can engender tumor growth attenuation.…”

Section: Discussionmentioning

confidence: 99%

Evidence for Stimulation of Tumor Proliferation in Cell Lines and Histotypic Cultures by Clinically Relevant Low Doses of the Galactoside-Binding Mistletoe Lectin, A Component of Proprietary Extracts

Gabius¹,

Darro²,

Remmelink³

et al. 2001

Cancer Investigation

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The toxic galactoside-specific lectin from mistletoe, a component of proprietary extracts with unproven efficacy in oncology, exhibits capacity to trigger enhanced secretion of proinflammatory cytokines at low doses (ng/ml or ng/kg body weight) and reductions of cell viability with increasing concentrations. To infer any tumor selectivity of this activity, cytofluorimetric and cell growth assays with a variety of established human tumor cell lines were performed. Only quantitative changes were apparent, and the toxicity against tumor cells was within the range of that of the tested fibroblast preparations from 5 donors. No indication for any tumor selectivity was observed. In kinetic studies with 8 sarcoma and 4 melanoma lines, this evidence for quantitative variability of the response in interindividual comparison was further underscored. At 50 pg lectin/ml x 10(5) cells, even a growth-stimulatory impact was noted in 5 of 12 tested cases. To mimic in vivo conditions with presence of cytokine-secreting inflammatory and stromal cells, exposure to the lectin was extended to histotypic cultures established from 30 cases of surgically removed tumor. As salient result, 5 specimens from 4 of the 8 tested tumor classes responded with a significant increase of [3H]-thymidine incorporation relative to controls during the culture period of 72 hours, when the lectin was present at a concentration in the described immunomodulatory range (1 ng/ml). A relation of this activity to the extent of the actual proliferative status of the reactive samples could not be delineated. Therefore, a non-negligible percentage of the established tumor cell lines (e.g., 3 from 8 sarcoma lines) can be markedly stimulated by the lectin at a very low dose and with dependence on the cell type. Furthermore, the feasibility to elicit a significant growth enhancement is likewise documented for human tumor explants in 16.6% of the examined cases. In view of the uncontrolled application of lectin-containing extracts in alternative/complementary medicine, the presented results on unquestionably adverse lectin-dependent effects in two culture systems call for rigorous examination of the clinical safety of this unconventional, scientifically entirely experimental treatment modality.

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Section: Discussionmentioning

confidence: 99%

Evidence for Stimulation of Tumor Proliferation in Cell Lines and Histotypic Cultures by Clinically Relevant Low Doses of the Galactoside-Binding Mistletoe Lectin, A Component of Proprietary Extracts

Gabius¹,

Darro²,

Remmelink³

et al. 2001

Cancer Investigation

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“…As alluded to earlier, the view that all cytokines are directly tumoricidal is no longer acceptable. Immune-cell-derived cytokines, such as IL-1 (Tsai and Gaffney, 1987), IL-6 (Miki et al, 1989) and TNFa (Wu et al, 1993), can directly stimulate turnour cells, lending support to the irnmunofacilitation theory of turnour growth (Prehn and Prehn, 1989). However, with the discovery that human non-lymphoid tumour cells are capable of producing cytokines, the possibility exists for an autocrine stimulation of tumour growth (Miki et al, 1989;Wu et al, 1993).…”

Section: Effects Of Ril-2 On Proliferationmentioning

confidence: 98%

Interleukin 2 receptor expression and interleukin 2 localisation in human solid tumour cells in situ and in vitro: Evidence for a direct role in the regulation of tumour cell proliferation

Kernohan

Flett

et al. 1995

Intl Journal of Cancer

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Frozen sections of 52 human solid tumours (38 malignant and 14 benign) of varied histogenesis were immunohistochemically stained with well characterised monoclonal antibodies (MAbs) to human interleukin 2 (IL-2) and the alpha and beta chains of its receptor (R). In all malignant specimens, the tumour cells expressed the IL-2R beta subunit (p75) but not the IL-2R alpha subunit (CD25). In 36 of 38 malignant tumours examined, there was conspicuous staining for IL-2 in the tumour cell nuclei/nucleoli and perinuclear cytoplasm. In the human solid tumour cell lines G361 (melanoma), A549 (lung), MCF-7 (breast) and WiDR (colorectal), both subunits of the IL-2R appeared to be expressed, although the alpha subunit only weakly. Exogenous addition of human recombinant (r) interleukin 2 altered cell numbers in 3 of the 4 cell lines (WiDR was refractory). When grown in the absence of exogenously added rIL-2, IL-2 staining was observed in all cell lines. The pattern of distribution was similar to that exhibited by the tumour cells in situ (i.e., a nuclear/nucleolar localisation). In G361 melanoma cells, this IL-2 staining was present in proliferating cells but disappeared as the cultures approached confluence. Addition of an IL-2R beta subunit blocking antibody to growing G361 cultures (grown in the absence of rIL-2) resulted in a significant reduction in cell numbers. We propose, therefore, that the presence of immunoreactive IL-2 and IL-2R expression is characteristic of human malignant cells and that IL-2 may play a role in the autocrine stimulation of proliferation of malignant cells, such as G361 melanoma cells.

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“…These, as well as many other observations [31,32] , challenge the widely held immune-surveillance hypothesis. A developing immune-response to a tumor probably must, regardless of the ultimate immunogenicity of the tumor, be weak before it grows strong.…”

Section: Immune Dependencymentioning

confidence: 80%

Cancer may be caused by the Immune Reaction

Prehn¹

2008

American J. of Pharmacology and Toxicology

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Hormesis-like effects of immunity have been documented during tumor-growth experiments in mice, quantitatively large immune-reactions have inhibited while lesser quantities of the same specific immune-reactants have been stimulatory to the growth of implanted tumors. Likewise, carcinogenesis has been inhibited by a high quantities of immune reactants, but positively stimulated by lower levels of the same reactants. One observation suggests that malignant transformation may seldom, if ever, occur in vivo if there is no immune reaction against the incipient neoplasm. These and many similar observations suggest a real danger that some vaccines might stimulate rather than inhibit tumor growth. These hormesis-like effects may help to provide explanations for a number of otherwise perplexing observations such as the following: (1): The fact that immunodepression for heart or kidney allografting results in an increased incidence of some tumors, especially leukemias and skin tumors, while others, such as those of breast and rectum, show a decreased incidence in these immunodepressed patients, (2): The possible dependency of carcinogenesis on an immune reaction, (3): The fact that adult Down's syndrome patients are unexpectedly resistant to solid tumors, especially breast-carcinoma, but have a very high incidence of leukemia, (4): The fact that Kaposi's sarcoma in an AIDS-patient often tends to flare as the patient's disease is ameliorated, (5): The sneaking through phenomenon, (6): Lastly, some peculiarities in the metastatic patterns of tumors of various types.

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The Flip Side of Tumor Immunity

Cited by 18 publications

References 41 publications

Evidence for Stimulation of Tumor Proliferation in Cell Lines and Histotypic Cultures by Clinically Relevant Low Doses of the Galactoside-Binding Mistletoe Lectin, A Component of Proprietary Extracts

Evidence for Stimulation of Tumor Proliferation in Cell Lines and Histotypic Cultures by Clinically Relevant Low Doses of the Galactoside-Binding Mistletoe Lectin, A Component of Proprietary Extracts

Interleukin 2 receptor expression and interleukin 2 localisation in human solid tumour cells in situ and in vitro: Evidence for a direct role in the regulation of tumour cell proliferation

Cancer may be caused by the Immune Reaction

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