Peripheral Blood CD4+ T-Cell Response Before Postoperative Active Immunotherapy Correlates with Clinical Outcome in Metastatic Melanoma

Hsueh, Eddy C.; Famatiga, Estela; Shu, Sherry T.; Ye, Xing; Morton, Donald L.

doi:10.1245/aso.2004.02.018

Cited by 21 publications

(11 citation statements)

References 34 publications

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“…The utility of Th2 cells or IL-4 as anti-tumor effectors has been reported by others, and in some cases Th2 cells were more effective than Th1 cells in the clearance of cytotoxic T lymphocyte-resistant tumors [10]. Furthermore, a human clinical trial of Canvaxin, a cell-based vaccine, found that the magnitude of vaccine-induced Th2 immunity correlated with overall survival, and anti-tumor Th2 cells can be identified in cancer patients supporting the possibility of generating such populations in humans [30,31]. As discussed above, we did not observe any influence of STAT6 signaling on the differentiation of DCT-specific CD4 1 T cells, suggesting that STAT6 is also required downstream of the effector CD4 1 T cells.…”

Section: Wt Vssupporting

confidence: 58%

CD4⁺ T‐cell‐mediated anti‐tumor immunity can be uncoupled from autoimmunity via the STAT4/STAT6 signaling axis

et al. 2009

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Previous reports have suggested that autoimmune sequelae may be an unavoidable consequence of successful immunization against tumor-associated antigens, which are typically non-mutated self-antigens. Using a melanoma model, we demonstrated that CD4 1 T-cell-mediated anti-tumor immunity and autoimmunity could be separated by modulating the STAT4/STAT6 signaling axis. Our results have revealed an unexpected dichotomy in the effector phase following cancer vaccination where anti-tumor immunity is mediated via a STAT6 and IL-4-dependent pathway, whereas autoimmune pathology is mediated via STAT4 through a mechanism that relies partially on IFN-c. Our results offer a possibility to elicit specific anti-tumor responses without triggering unwanted tissue autoimmune diseases.

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Section: Wt Vssupporting

confidence: 58%

CD4⁺ T‐cell‐mediated anti‐tumor immunity can be uncoupled from autoimmunity via the STAT4/STAT6 signaling axis

et al. 2009

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“…However, the correlation between the development of strong DTH response to melanoma cells and improved survival of vaccinated melanoma patients as seen by us, as well as several other whole-cell vaccine studies, implies the opposite (52)(53)(54)(55)(56). Furthermore, DTH response is a reliable clinical parameter that reflects the overall immune response to other vaccines, including peptides (32) and dendritic cell-based vaccines (53), and can be applied in vaccination protocol as an efficient and available immunologic tool.…”

Section: Discussionmentioning

confidence: 69%

Autologous Melanoma Vaccine Induces Antitumor and Self-Reactive Immune Responses That Affect Patient Survival and Depend on MHC Class II Expression on Vaccine Cells

Lotem

Machlenkin

Hamburger

et al. 2009

Clinical Cancer Research

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Purpose: Autologous melanoma cells display a broad variety of tumor antigens and were used for treatment of American Joint Committee on Cancer stages III and IV melanoma as an adjuvant or active therapy. Survival data and immune response were evaluated in vaccinated patients. Experimental Design: Forty-seven patients received 2,4-dinitrophenyl–conjugated autologous melanoma vaccine as an adjuvant (23 patients) or therapy (24 patients). CD4 and CD8 T-cell response in blood sampled before vaccination and after five or eight vaccine doses was evaluated against melanoma cells and autologous peripheral blood mononuclear cells using IFNγ enzyme–linked immunospot. Serum levels of antilivin, an inhibitor of apoptosis, and anti-gp100 IgG were determined. Results: The immunologic effect of the vaccine differed between the two groups of patients. In the adjuvant group, there was a significant increase in CD8 melanoma-reactive T cells (P = 0.035) after vaccination and an increase in antimelanoma CD4 T cells correlating with improved overall survival (P = 0.04). In the therapeutic group, there was no objective tumor regression; antimelanoma T-cell reactivity increased by a small amount, stayed the same, or in some cases decreased. In all patients, a significant increase was noted in CD4 T-cell reactivity against autologous peripheral blood mononuclear cells (P = 0.02), which did not affect survival. Increased antilivin IgG was associated with improved survival. Expression of MHC class II on melanoma cells was vital for the immunogenicity of the vaccine. Conclusion: Autologous melanoma cell vaccine is capable of inducing effective antimelanoma CD4 T-cell activity associated with improved survival. Patients with active metastatic disease generally displayed reduced immune response and gained little from active immunization.

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“…Some investigations have reported that Th2 cells are more advantageous compared with Th1 cells in the eradication of CTL-resistant tumors [ 9 , 10 ]. A human clinical trial on a vaccine also showed that overall recovery from cancer is related to the ratio of vaccine-induced Th2 immunity and antitumor Th2 cells can be found in cancer patients [ 10 , 23 , 24 ]. Based on these data showing the potential importance of CD4 + T cells combined with Th2-related antitumor cytokine interactions in tumor clearance, we investigated how these diverse mechanisms interact with periodically pulsed therapies to dictate the antitumor function in this setting.…”

Section: The Mathematical Modelmentioning

confidence: 99%

Periodically Pulsed Immunotherapy in a Mathematical Model of Tumor, CD4⁺ T Cells, and Antitumor Cytokine Interactions

Wei

Hsu

2017

Computational and Mathematical Methods in Medicine

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Immunotherapy is one of the most recent approaches for controlling and curing malignant tumors. In this paper, we consider a mathematical model of periodically pulsed immunotherapy using CD4+ T cells and an antitumor cytokine. Mathematical analyses are performed to determine the threshold of a successful treatment. The interindividual variability is explored by one-, two-, and three-parameter bifurcation diagrams for a nontreatment case. Numerical simulation conducted in this paper shows that (i) the tumor can be regulated by administering CD4+ T cells alone in a patient with a strong immune system or who has been diagnosed at an early stage, (ii) immunotherapy with a large amount of an antitumor cytokine can boost the immune system to remit or even to suppress tumor cells completely, and (iii) through polytherapy the tumor can be kept at a smaller size with reduced dosages.

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Peripheral Blood CD4+ T-Cell Response Before Postoperative Active Immunotherapy Correlates with Clinical Outcome in Metastatic Melanoma

Cited by 21 publications

References 34 publications

CD4⁺ T‐cell‐mediated anti‐tumor immunity can be uncoupled from autoimmunity via the STAT4/STAT6 signaling axis

CD4⁺ T‐cell‐mediated anti‐tumor immunity can be uncoupled from autoimmunity via the STAT4/STAT6 signaling axis

Autologous Melanoma Vaccine Induces Antitumor and Self-Reactive Immune Responses That Affect Patient Survival and Depend on MHC Class II Expression on Vaccine Cells

Periodically Pulsed Immunotherapy in a Mathematical Model of Tumor, CD4⁺ T Cells, and Antitumor Cytokine Interactions

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Peripheral Blood CD4+ T-Cell Response Before Postoperative Active Immunotherapy Correlates with Clinical Outcome in Metastatic Melanoma

Cited by 21 publications

References 34 publications

CD4+ T‐cell‐mediated anti‐tumor immunity can be uncoupled from autoimmunity via the STAT4/STAT6 signaling axis

CD4+ T‐cell‐mediated anti‐tumor immunity can be uncoupled from autoimmunity via the STAT4/STAT6 signaling axis

Autologous Melanoma Vaccine Induces Antitumor and Self-Reactive Immune Responses That Affect Patient Survival and Depend on MHC Class II Expression on Vaccine Cells

Periodically Pulsed Immunotherapy in a Mathematical Model of Tumor, CD4+ T Cells, and Antitumor Cytokine Interactions

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Resources

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CD4⁺ T‐cell‐mediated anti‐tumor immunity can be uncoupled from autoimmunity via the STAT4/STAT6 signaling axis

CD4⁺ T‐cell‐mediated anti‐tumor immunity can be uncoupled from autoimmunity via the STAT4/STAT6 signaling axis

Periodically Pulsed Immunotherapy in a Mathematical Model of Tumor, CD4⁺ T Cells, and Antitumor Cytokine Interactions