Cryosurgical ablation of liver tumors in colon cancer patients increases the serum total ganglioside level and then selectively augments antiganglioside IgM

Ravindranath, Mepur H.; Wood, Tabitha E.; Soh, Daniel; Gonzales, Alexandra; Muthugounder, Sakunthala; Pérez, Carlos A.; Morton, Donald L.; Bilchik, Anton J.

doi:10.1016/s0011-2240(02)00102-5

Cited by 42 publications

(31 citation statements)

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“…[1][2][3][4] Pancreatic adenocarcinoma and hepatic metastases of colorectal carcinomas express GD3 poorly but overexpress GM2, GD1b and GT1b. 5,6,16 Third, during tumor cell proliferation and necrosis, the tumor-associated gangliosides may be released into the tumor microenvironment and enter into the circulation. Finally, circulating tumor-gangliosides suppress a variety of immunofunctions.…”

Section: Discussionmentioning

confidence: 99%

“…[8][9][10] Tumor-associated gangliosides, when shed into the circulation, [11][12][13][14][15] may elicit an endogenous IgM antibody response. 16 In patients with advanced colon cancer, cryoablation (freezing and thawing) of hepatic metastases causes tumor necrosis and releases tumor-associated gangliosides into the circulation. 16 Gangliosides released because of tumor necrosis augment IgM antibodies without the need for exogenous adjuvants.…”

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confidence: 99%

“…16 In patients with advanced colon cancer, cryoablation (freezing and thawing) of hepatic metastases causes tumor necrosis and releases tumor-associated gangliosides into the circulation. 16 Gangliosides released because of tumor necrosis augment IgM antibodies without the need for exogenous adjuvants. 16 Antiganglioside IgM antibodies occur naturally in healthy individuals, 17 but in cancer patients the level of antiganglioside antibodies varies according to the stage of disease and tumor progression.…”

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confidence: 99%

“…16 Gangliosides released because of tumor necrosis augment IgM antibodies without the need for exogenous adjuvants. 16 Antiganglioside IgM antibodies occur naturally in healthy individuals, 17 but in cancer patients the level of antiganglioside antibodies varies according to the stage of disease and tumor progression. 15,18 We hypothesize that the endogenous IgM response to gangliosides might be an early immunologic event of tumorigenesis.…”

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confidence: 99%

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Endogenous immune response to gangliosides in patients with confined prostate cancer

Ravindranath

Muthugounder

Presser

et al. 2005

Intl Journal of Cancer

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Our study investigated whether endogenous IgM antibodies to gangliosides occur in patients with early stages of prostate cancer (CaP) patients, after defining ganglioside profiles of CaP cell lines. Immune and resorcinol staining detected the presence of gangliosides GM3, GM2, GD3, GD2 and GD1a but not GM1a, GD1b or GT1b in the extracts of normal prostatic epithelial cells (PrEC) and neoplastic androgen‐insensitive (PC‐3, DU145) and ‐sensitive (LNCaP‐FGC and LNCaP‐FGC‐10) CaP cells. Using a sensitive ELISA, developed and validated in our laboratory, the titers of IgM against 8 gangliosides from sera of patients with benign prostatic hyperplasia (BPH) (n = 11), organ‐confined (T1/T2, n = 36) and unconfined (T3/T4, n = 27) CaP and age‐matched healthy men (n = 11) were determined double‐blinded. Using ANOVA and Fisher's least significant difference (LSD) methods, the log‐titers among different groups were compared. CaP patients differed from healthy and BPH patients in increased titers against GD1a and decreased titers against GD3. Titers of antibodies to other gangliosides exhibited no difference between CaP patients and others. The specific augmentation of anti‐GD1a IgM in patients with organ‐confined CaP (stage T1/T2) but not in patients with unconfined CaP (stage T3/T4) or BPH or in healthy controls is striking. This finding together with identification of GD1a as a major ganglioside in CaP cell lines and with the accruing studies on the immunosuppressive nature of GD1a indicates that augmentation of anti‐GD1a IgM in confined CaP may signify an early endogenous immune response to eliminate a “danger signal” from tumor microenvironment and circulation. © 2005 Wiley‐Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Endogenous immune response to gangliosides in patients with confined prostate cancer

Ravindranath

Muthugounder

Presser

et al. 2005

Intl Journal of Cancer

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“…Other ablative tumor treatments have been shown to induce an anti-tumor IgM response (28). We characterized the humoral immune response monitoring the B cell pattern during RFA and the specific IgGs titers against the MUC1 tumor antigen and HCV capsidic proteins in metastatic and HCC patients, Elispot assay for evaluating the production of IFN-γ after stimulation with specific tumor-associated MUC1 glycopeptides before and after RFA in metastatic liver patients P1 (breast) and P9 (colon).…”

Section: Discussionmentioning

confidence: 99%

RFA strongly modulates the immune system and anti-tumor immune responses in metastatic liver patients

et al. 2008

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Abstract. Radiofrequency tumor ablation (RFA) is a therapeutic modality for liver cancer patients inducing localized tumor necrosis with maximal preservation of normal liver parenchyma. We investigated the immunomodulatory effects exerted by RFA treatment in liver cancer patients with metastatic liver lesions (13 patients) or hepatocellular carcinoma (HCC) (4 patients). Analysis of lymphocyte subsets by flow cytometry revealed that after RFA, CD3 + T cells, in particular CD4 + , were decreased in metastatic cancer patients, while no change was observed in HCC patients. Moreover, RFA induced trafficking of naïve and memory CD62L + T cells from circulation to tissues. When characterizing the function of T cells, proliferative response to PHA was strongly increased after 48 h from RFA in metastatic cancer patients. Furthermore, T cells produced IFN-γ in response to the tumor associated MUC1 antigen. In contrast, humoral immune responses against tumor antigens such as MUC1 and HCV proteins were unaffected by RFA treatment, although increase of circulating B cells was observed only in metastatic cancer patients. These results indicate that RFA application can exert an activating effect on the immune system in metastatic cancer patients, favouring trafficking of lymphocyte subsets and enhancing tumor antigen specific cellular immune responses.

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Monitoring response to treatment in melanoma patients: Potential of a serum glycomic marker

Selvan

Dillman

Fowler

et al. 2007

Intl Journal of Cancer

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A mechanistic marker correlating with tumor progression and clinical response is useful for assessing therapeutic response and determining the course of therapy. Since serum-total-ganglioside (sTG) and antiganglioside-IgM antibody levels reflected tumor progression, the feasibility of utilizing sTG for assessing the response to immunotherapy of metastatic-melanoma was tested. Patients (n 5 34) were immunized with dendritic cells cocultured with irradiated, IFNc-treated autologous tumor cells admixed with GM-CSF. Levels of sTG and antiganglioside-IgM antibody titers were measured in sera of vaccine recipients at 0, 4 and 24 weeks of treatment. Based on sTG-level, whether lower (L) or higher (H) than the mean 1 1 SD of normal and healthy volunteers on weeks 0, 4 and 24, patients were categorized into cohorts-I (LLL, n 5 16), II (HHL/HLL, n 5 4), III (LLH/LHH/LHL, n 5 7) and IV (HHH/HLH, n 5 7). The cohorts were regrouped as sTG-downregulators (sTG-DR; n 5 20) and upregulators (sTG-UR; n 5 14). These two cohorts differed significantly in their overall (p < 0.012) and progression-free (p 5 0.0001) survival posttreatment. 43% sTG-UR died within 39 months, with a median survival of 39 months, whereas 61% of the sTG-DR survived for 48 months. Both endogenous and vaccine-induced antigangliosideIgM antibodies appeared to regulate sTG levels. Nonresponders had increased sTG with no or low IgM antibody response. The sTG level is regulated within 24 weeks post-treatment and therefore, may serve as an ideal biomarker for assessing therapeutic responses in patients. Clinical correlations of sTG indicate that sTG-downregulating therapy may be an effective treatment strategy for melanoma. ' 2007 Wiley-Liss, Inc.

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Cryosurgical ablation of liver tumors in colon cancer patients increases the serum total ganglioside level and then selectively augments antiganglioside IgM

Cited by 42 publications

References 50 publications

Endogenous immune response to gangliosides in patients with confined prostate cancer

Endogenous immune response to gangliosides in patients with confined prostate cancer

RFA strongly modulates the immune system and anti-tumor immune responses in metastatic liver patients

Monitoring response to treatment in melanoma patients: Potential of a serum glycomic marker

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