Immunological consequences of tumor excision: From active immunity to immunological memory

Bursuker, Isia; North, Robert J.

doi:10.1002/ijc.2910370216

Cited by 19 publications

(19 citation statements)

References 14 publications

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“…In our model, we were unable to find any evidence of a phenomenon described as concomitant immunity 18 in which surgical debulking is reported to result in a slower growth Figure 5. Surgical and distal site tumor growth after debulking surgery and vaccination with AC29 -GM -CSF 1.6, AC29 -B7 -1, and AC29 -IL -4 simultaneously.…”

Section: Discussionmentioning

confidence: 56%

“…18,19 We therefore hypothesized that debulking (cytoreductive ) surgery, if combined with immunological gene therapy using tumor transfectants containing immunologically active molecules (including cytokines and molecules involved in antigen presentation and T cell stimulation) , would generate a more effective systemic antitumor response than either treatment alone. We performed this study using a welldescribed murine model of MM that demonstrates all the histological and pathological features of the human disease and like most solid tumors is nonimmunogenic.…”

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confidence: 99%

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The immune anti-tumor effects of GM-CSF and B7-1 gene transfection are enhanced by surgical debulking of tumor

et al. 2001

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Malignant mesothelioma ( MM ) is a solid tumor largely unresponsive to conventional therapies. Immunological gene therapy shows promise in murine models and human clinical trials; however, the role of surgery in combination with gene therapy has not been widely studied. The aim of this study was to determine if debulking surgery improved the effectiveness of gene therapy in a murine MM model. Mice were subcutaneously inoculated with the MM cell line, AC29, at two different sites, 4 days apart, to allow a surgical and distal site tumor to develop. Once tumors were established, the surgical site tumor was debulked and vaccination of syngeneic tumor transfectants encoding genes for IL -4, IL -2, GM -CSF, B7 -1 or allogeneic MHC molecules commenced at a site away from both tumors, and tumor growth was measured. Neither debulking surgery nor gene therapy alone delayed tumor growth. However, there was a clear delay of tumor growth when debulking surgery was combined with vaccination of tumor transfectants expressing B7 -1 or high levels of GM -CSF. Combinations of these two transfectants did not lead to a synergistic effect. This study demonstrates that debulking surgery can augment the immunostimulatory effects of immunological gene therapy and can delay tumor growth. This has implications for the future design of human gene therapy trials for solid tumors such as MM.

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Section: Discussionmentioning

confidence: 56%

mentioning

confidence: 99%

The immune anti-tumor effects of GM-CSF and B7-1 gene transfection are enhanced by surgical debulking of tumor

et al. 2001

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“…Early in the growth of some methylcholanthrene-induced tumours, splenic T cells and macrophages are responsible for killing tumour cells in vitro, whereas in animals with large tumours splenic immunity is dependent on B cells (38). T cell-mediated immunity generated by Corynebacterium parvuw-induced tumour regression (39), or tumour excision (40), is sensitive to cyclophosphamide treatment if spleens are collected from donors shortly after initiation of immunity, but not so if collected two to three weeks later. Immunity detectable two days after excision of Meth A fibrosarcomas is mediated by Ly l-(iow)2+ T cells, whereas 2 weeks later anti-tumour immunity is mediated by Ly 1+2+ cells, or possibly by a combination of Ly 1+2-and Ly l-(iow)2+ cells (40).…”

Section: Discussionmentioning

confidence: 99%

“…T cell-mediated immunity generated by Corynebacterium parvuw-induced tumour regression (39), or tumour excision (40), is sensitive to cyclophosphamide treatment if spleens are collected from donors shortly after initiation of immunity, but not so if collected two to three weeks later. Immunity detectable two days after excision of Meth A fibrosarcomas is mediated by Ly l-(iow)2+ T cells, whereas 2 weeks later anti-tumour immunity is mediated by Ly 1+2+ cells, or possibly by a combination of Ly 1+2-and Ly l-(iow)2+ cells (40). North (40) has interpreted these changes in his model as reflecting the emergence of memory cells.…”

Section: Discussionmentioning

confidence: 99%

“…Immunity detectable two days after excision of Meth A fibrosarcomas is mediated by Ly l-(iow)2+ T cells, whereas 2 weeks later anti-tumour immunity is mediated by Ly 1+2+ cells, or possibly by a combination of Ly 1+2-and Ly l-(iow)2+ cells (40). North (40) has interpreted these changes in his model as reflecting the emergence of memory cells.…”

Section: Discussionmentioning

confidence: 99%

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Differences in the phenotypes of cells mediating anti‐tumour immunity at various stages of tumour progression in mice

et al. 1989

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Summary In Winn assays, T cells from donors immunized by tumour excision, or from mice with small tumours, mediate rejection of the metastasizing murine fibrosarcoma MC‐2. As the mean size of primary tumours in spleen donors increases, the strength of anti‐tumour activity declines, until it is frequently undetectable in spleen cells from mice with very large tumour burdens. Loss of splenic anti‐tumour activity is coincident with the appearance of cells capable of suppressing an otherwise protective anti‐tumour response in Winn assays. This paper defines the phenotypes of T cells mediating immunity against MC‐2. Eleven or more days after tumour inoculation the proportions of tumour‐bearer splenic leucocytes expressing Ly 1.2 (CD5), Ly 2.2 (CD8a) or L3T4 (CD4) surface antigens were significantly less than similar preparations from normal animals. Depletion of Ly 1.2+ or L3T4+ cells from spleen cells of donors with small tumours, or from donors immunized by tumour excision, diminished protection in the Winn assay. Depletion of Ly 2.2+ cells from these donors had no effect on immunity. In contrast, spleen cells taken from donors with large tumours lost all anti‐tumour activity if pretreated with any one of anti‐Ly 1.2 or anti‐Ly 2.2 or anti‐L3T4 antibodies in the presence of complement. These results suggest that cells bearing the Ly 2.2 marker may be important to weak immunity remaining in the spleens of mice with large tumours, but are not critical to strong immunity generated early in tumour growth, nor to that following tumour excision. That is, in addition to an Ly 1.2+, Ly 2.2−, L3T4+ spleen cell subset also seen early in the growth of the MC‐2 tumour, a cell population which expresses the Ly 2.2 marker and which is important to anti‐tumour immunity emerges late in tumour growth.

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Immunomodulation in an apparently non‐immunogenic murine tumor

Bursuker

Petty

Neddermann

et al. 1991

Intl Journal of Cancer

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Madison lung carcinoma (M109), a murine tumor of spontaneous origin, appears to be non-immunogenic, according to 2 commonly employed tests for tumor immunogenicity. However, C.parvum-induced immunopotentiation during the growth of M109 tumor results in post-excision anti-tumor immunity to M109 tumor implants. The C.parvum-potentiated post-excision immunity to M109 is tumor-specific and T-cell-dependent. T cells from mice whose progressive M109 tumors have been excised are capable, on passive transfer, of inhibiting adoptive immunotherapy of T-cell-deficient recipients by spleen cells from mice immunized with an admixture of M109 cells and C.parvum. The data are interpreted as evidence supporting the hypothesis that the apparent lack of anti-tumor immunity in this tumor model is not due to the absence of tumor-associated antigens. We suggest that, instead, in this model the balance between the effector and suppressor arms of the immune response favors tumor-induced immunosuppression, resulting in a magnitude of anti-tumor immunity insufficient for detection by commonly employed tests for tumor immunogenicity. Our study shows that shifting the balance in favor of the effector arm by means of immunopotentiation results in a measurable immune response to an apparently non-immunogenic tumor.

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Immunological consequences of tumor excision: From active immunity to immunological memory

Cited by 19 publications

References 14 publications

The immune anti-tumor effects of GM-CSF and B7-1 gene transfection are enhanced by surgical debulking of tumor

The immune anti-tumor effects of GM-CSF and B7-1 gene transfection are enhanced by surgical debulking of tumor

Differences in the phenotypes of cells mediating anti‐tumour immunity at various stages of tumour progression in mice

Immunomodulation in an apparently non‐immunogenic murine tumor

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