Natural cytotoxicity in lymphatic metastasis

Matzku, S.; Oberneder, Hans-Peter; Keller, R.; Zöller, Margot

doi:10.1007/bf00200044

Cited by 8 publications

(2 citation statements)

References 40 publications

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“…NK activity, evaluated against highly NK-susceptible AS cells [34] was most strongly supported by ASML-exosomes in response to IL2. When co-cultured with NK-enriched NKR-P1B + SC, even 10 μg/ml ASML-exosomes sufficed for an increase in cytotoxic activity.…”

Section: Resultsmentioning

confidence: 99%

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Tumor-exosomes and leukocyte activation: an ambivalent crosstalk

et al. 2012

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BackgroundTumor-exosomes being reported to suppress or promote a cancer-directed immune response, we used exosomes of the rat pancreatic adenocarcinoma BSp73ASML (ASML) to evaluate, whether and which steps in immune response induction can be affected by tumor-exosomes and how the impaired responsiveness can be circumvented.ResultsASML-exosomes bind to and are taken up by all leukocyte subpopulations in vivo and in vitro, uptake by CD11b+ leukocytes exceeding that by T and B cells. ASML-exosomes affect leukocyte proliferation via reduced CD44v6 up-regulation and lck, ZAP70 and ERK1,2 phosphorylation, which can be compensated by dendritic cells (DC). ASML-exosomes do not support Treg. Yet, impaired activation of anti-apoptotic signals is accompanied by slightly increased apoptosis susceptibility. IgM secretion is unaffected; NK and CTL activity are strengthened, ASML-exosomes co-operating with DC in CTL activation. ASML-exosomes transiently interfere with leukocyte migration by occupying migration-promoting receptors CD44, CD49d, CD62L and CD54 during binding/internalization.ConclusionASML-exosomes might well serve as adjuvant in immunotherapy as they support leukocyte effector functions and have only a minor impact on leukocyte activation, which can be overridden by DC. However, exosome-induced modulation of immune cells relies, at least in part, on exosome uptake and message transfer. This implies that depending on the individual tumor's exosome composition, exosomes may distinctly affect the immune system. Nonetheless, whether immunotherapy can profit from using tumor-exosomes as adjuvant can easily be settled beforehand in vitro.

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Section: Resultsmentioning

confidence: 99%

“…Confluent cultures were detached with trypsine or EDTA and split. ASML cells are NK resistant, AS cells are highly NK susceptible [34]. …”

Section: Methodsmentioning

confidence: 99%

Tumor-exosomes and leukocyte activation: an ambivalent crosstalk

et al. 2012

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Interferon‐gamma treatment of B16 melanoma cells: Opposing effects for non‐adaptive and adaptive immune defense and its reflection by metastatic spread

Zöller

Strubel

Hämmerling

et al. 1988

Intl Journal of Cancer

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The impact of interferon-gamma (IFN) treatment of tumor cells on non-adaptive and adaptive immune defense and its reflection by metastatic spread were evaluated using a weakly metastasizing variant of B16 melanoma (B16-FI). Treatment of B16-FI with IFN resulted in a decrease in binding structures for NK cells and concomitantly in augmented metastasizing capacity. In line with this, activation of NK cells and Mo, which led to reduction of metastatic nodes, was less efficient with IFN-treated B16-FI, while after elimination of non-adaptive immune defense, the number of metastases increased significantly, but irrespective of IFN treatment. On the other hand, IFN-treated B16-FI cells become more prone to killing by cytotoxic T-cells (CTL). This was due to increased lysability by CTL and to increased immunogenicity; i.e., a higher frequency of B16-specific CTL was observed after immunization with IFN-treated than with untreated B16-FI. The reverse phenomenon was observed with anomalous and/or lymphokine-activated killer cells (AK/LAK). The common cause of increased antigenicity and immunogenicity may reside in increased expression of class-I and de novo expression of class-II MHC antigens after IFN treatment. Increased antigenicity and immunogenicity of IFN-treated B16-FI was reflected by significant reduction of metastatic nodes, prolonged survival and increased TD100 in animals immunized with IFN-treated vs. untreated melanoma cells. Comparison of the divergent effects of IFN treatment on B16-FI melanoma cells showed that the benefit of increased antigenicity/immunogenicity clearly outweighed the disadvantage of reduced susceptibility to non-adaptive immune defense.

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Retardation of metastatic tumor growth after immunization with metastasis‐specific monoclonal antibodies

Reber

Matzku

Günthert

et al. 1990

Intl Journal of Cancer

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The influence of 4 murine monoclonal antibodies (MAbs) directed against surface determinants of a metastasizing rat adenocarcinoma (BSp73ASML) on metastatic spread was evaluated and compared to their in vivo binding as well as to the induction of a humoral anti-MAb response, especially with respect to the development of anti-idiotypic (ID) antibodies of the internal image type. In a protocol of explicit immunization, all 4 MAbs transiently inhibited metastatic growth. Survival was prolonged only with one MAb (4.4ASML). With another MAb (1.1ASML), directed against a new variant form of CD44, metastatic growth was accelerated after transient retardation. Retardation of metastatic growth correlated with the humoral anti-MAb response. This accounted for the isotype- as well as for the idiotype-specific response. An exception was noted after immunization with MAb 1.1ASML. Rats with high levels of anti-1.1ASML antibodies, which inhibited binding to the tumor cells (internal image-type antibodies) showed accelerated metastatic spread. Data are interpreted to mean that MAb-induced inhibition of metastatic spread may be based on 2 independent mechanisms: blockade of metastasis-associated epitopes (i.e., with MAb 1.1ASML) and induction of an anti-mouse Ig response. In the latter case it was irrelevant whether the response was isotype- or idiotype-specific.

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Natural cytotoxicity in lymphatic metastasis

Cited by 8 publications

References 40 publications

Tumor-exosomes and leukocyte activation: an ambivalent crosstalk

Tumor-exosomes and leukocyte activation: an ambivalent crosstalk

Interferon‐gamma treatment of B16 melanoma cells: Opposing effects for non‐adaptive and adaptive immune defense and its reflection by metastatic spread

Retardation of metastatic tumor growth after immunization with metastasis‐specific monoclonal antibodies

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