Analysis of Th1 and Th2 cytokine production by peripheral blood mononuclear cells as a parameter of immunological dysfunction in advanced cancer patients

Goto, Shigenori; Sato, Motonori; Kaneko, R; Itoh, Masayoshi; Sato, Shinobu; Takeuchi, Shoshichi

doi:10.1007/s002620050620

Cited by 89 publications

(71 citation statements)

References 28 publications

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“…Immune defects and dysfunction in T cells and the antigen presenting and stimulatory capacity of DC have previously been reported in cancer patients (Mizoguchi et al, 1992;Goto et al, 1999;Kiessling et al, 1999;Ninomiya et al, 1999). As in vitro expansion capacity is dependent upon both the number and stimulatory capacity of CDld antigenpresenting cells, reduced numbers of and/or functionally defective CDld APC may suppress NKT activation in cancer patients.…”

Section: Discussionmentioning

confidence: 97%

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Modulation of human Vα24+Vβ11+ NKT cells by age, malignancy and conventional anticancer therapies

Crough

Purdie²,

Okai³

et al. 2004

Br J Cancer

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Immunotherapy strategies aimed at increasing human Va24 þ Vb11 þ natural killer T (NKT) cell numbers are currently a major focus. To provide further information towards the goal of NKT cell-based immunotherapy, we assessed the effects of age, cancer status and prior anticancer treatment on NKT cell numbers and their expansion capacity following a-galactosylceramide (a-GalCer) stimulation. The percentage and absolute number of peripheral blood NKT cells was assessed in 40 healthy donors and 109 solid cancer patientsResponsiveness to a-GalCer stimulation was also assessed in 28 of the cancer patients and 37 of the healthy donors. Natural killer T cell numbers were significantly reduced in melanoma and breast cancer patients. While NKT numbers decreased with age in healthy donors, NKT cells were decreased in these cancer subgroups despite age and sex adjustments. Prior radiation treatment was shown to contribute to the observed reduction in melanoma patients. Although cancer patient NKT cells were significantly less responsive to a-GalCer stimulation, they remained capable of substantial expansion. Natural killer T cells are therefore modulated by age, malignancy and prior anticancer treatment; however, cancer patient NKT cells remain capable of responding to a-GalCer-based immenotherapies.

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Section: Discussionmentioning

confidence: 97%

“…As the ageing process and immune dysfunction due to malignant disease have been shown to impact other cell types, these factors require consideration for NKT cells (Goto et al, 1999;Ninomiya et al, 1999;Hakim et al, 2004;Plackett et al, 2004).…”

mentioning

confidence: 99%

Modulation of human Vα24+Vβ11+ NKT cells by age, malignancy and conventional anticancer therapies

Crough

Purdie²,

Okai³

et al. 2004

Br J Cancer

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show abstract

“…Our data support these studies, because combination therapy in the TRAMP model of spontaneous prostate adenocarcinoma was effective only when administered with a vaccine against a tumor-associated antigen. Moreover, because the induction of Th2 cytokines by aOX40/ aCTLA-4 limited the effectiveness of this therapy, using a vaccine strategy to target cross-presenting dendritic cells specifically should preferentially skew the response away from a Th2 T-cell response and toward a Th1 CD4 T-cell response, which is more favorable for tumor regression and patient survival (54)(55)(56)(57). The use of anti-DEC-205 mAb conjugated to NY-ESO-1 in patients with solid tumors (NCT01522820) finished testing with promising results (19) and currently is being tested clinically in patients with acute myeloid leukemia (NCT01834248).…”

Section: Images Depict Sections Of Paraffin-embedded Slides Stained Umentioning

confidence: 99%

Combination OX40 agonism/CTLA-4 blockade with HER2 vaccination reverses T-cell anergy and promotes survival in tumor-bearing mice

Linch

Kasiewicz

McNamara

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Immunotherapy is gathering momentum as a primary therapy for cancer patients. However, monotherapies have limited efficacy in improving outcomes and benefit only a subset of patients. Combination therapies targeting multiple pathways can augment an immune response to improve survival further. Here, we demonstrate that dual aOX40 (anti-CD134)/aCTLA-4 (anti-cytotoxic T-lymphocyte-associated protein 4) immunotherapy generated a potent antigen-specific CD8 T-cell response, enhancing expansion, effector function, and memory T-cell persistence. Importantly, OX40 and CTLA-4 expression on CD8 T cells was critical for promoting their maximal expansion following combination therapy. Animals treated with combination therapy and vaccination using anti-DEC-205 (dendritic and epithelial cells, 205 kDa)-HER2 (human epidermal growth factor receptor 2) had significantly improved survival in a mammary carcinoma model. Vaccination with combination therapy uniquely restricted Th2-cytokine production by CD4 cells, relative to combination therapy alone, and enhanced IFNγ production by CD8 and CD4 cells. We observed an increase in MIP-1α (macrophage inflammatory protein-1α)/CCL3 [chemokine (C-C motif) ligand 3], MIP-1β/CCL4, RANTES (regulated on activation, normal T-cell expressed and excreted)/CCL5, and GM-CSF production by CD8 and CD4 T cells following treatment. Furthermore, this therapy was associated with extensive tumor destruction and T-cell infiltration into the tumor. Notably, in a spontaneous model of prostate adenocarcinoma, vaccination with combination therapy reversed anergy and enhanced the expansion and function of CD8 T cells recognizing a tumor-associated antigen. Collectively, these data demonstrate that the addition of a vaccine with combined aOX40/aCTLA-4 immunotherapy augmented antitumor CD8 T-cell function while limiting Th2 polarization in CD4 cells and improved overall survival.

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“…The cytokine response by normal anti-CD3-activated lymphocytes was similar to levels described elsewhere. 42 The specificity of the changes for H-ferritin was examined by addition of rH02 to the supernatants. As shown in Table II, the MAb reversed the effects of the supernatants on the increased production of IL-10 and IFN-␥ and the suppression of IL-2 and IL-4 production.…”

Section: Mechanism Of Anti-proliferative Effects Of H-ferritin On Antmentioning

confidence: 99%

Immunosuppressive effects of melanoma-derived heavy-chain ferritin are dependent on stimulation of IL-10 production

et al. 2001

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Analysis of Th1 and Th2 cytokine production by peripheral blood mononuclear cells as a parameter of immunological dysfunction in advanced cancer patients

Abstract: Patients with advanced cancer are deficient in monocytes and the type 1 immune response. The measurement of various cytokines reported in this study provides a more sensitive and valuable tool for evaluating the function of cell-mediated immunity in cancer patients than do the usual tests.

Cited by 89 publications

References 28 publications

Modulation of human Vα24+Vβ11+ NKT cells by age, malignancy and conventional anticancer therapies

Modulation of human Vα24+Vβ11+ NKT cells by age, malignancy and conventional anticancer therapies

Combination OX40 agonism/CTLA-4 blockade with HER2 vaccination reverses T-cell anergy and promotes survival in tumor-bearing mice

Immunosuppressive effects of melanoma-derived heavy-chain ferritin are dependent on stimulation of IL-10 production

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