Th1/Th2 balance in cancer, transplantation and pregnancy

Shurin, Michael R.; Liu, Lu; Kaliński, Paweł; Stewart‐Akers, Ann M.

doi:10.1007/s002810050071

Cited by 36 publications

(40 citation statements)

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“…Shurin et al summarized the data from plenty of clinical studies that investigated Th1/Th2 balance in cancer patients. They found IL-4, as well as other Th2 cytokines, was usually up-regulated in patients with different types of cancers, such as renal cell cancer, non-small lung cancer, prostate cancer, colon cancer, breast cancer and other types of tumors (15). Onishi et al even found the IL-4 amount at tumor site was associated with the stage and grade of renal cancer (16).…”

Section: The Paradox Of Il-4 In Tumor Immunitymentioning

confidence: 99%

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Paradoxical Roles of IL-4 in Tumor Immunity

2009

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Section: The Paradox Of Il-4 In Tumor Immunitymentioning

confidence: 99%

“…Since the discovery of Th1 and Th2 cells by Mosmann in 1986 (31), their impacts on infection, allergy, autoimmune disease and transplantation etc have been extensively studied (15). In tumor immunity, Th2-dorminant immune response often fails to protect hosts from tumor growth.…”

Section: Endogenous Il-4 Deviates Host Immune Response To An Ineffectmentioning

confidence: 99%

Paradoxical Roles of IL-4 in Tumor Immunity

2009

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“…STAT6 Ϫ/Ϫ mice are deficient in responsiveness to IL-4 and IL-13, two cytokines essential for development of CD4 ϩ Th2 cells, and hence preferentially produce CD4 ϩ Th1 cells (4 -6). It has been hypothesized that the development of Th1 cells optimizes CD8-mediated tumor immunity (7), and hence STAT6 Ϫ/Ϫ mice were thought to be more tumor resistant because they predominantly make Th1 cells. In vivo depletion studies in the mammary carcinoma system, however, contradicted this hypothesis and demonstrated that although CD8 ϩ T cells are essential for tumor rejection by STAT6 Ϫ/Ϫ mice, CD4 ϩ T cells are not involved (3).…”

Section: Ice With a Deleted Stat6 Gene (Stat6 ϫ/ϫ Mice)mentioning

confidence: 99%

Resistance to Metastatic Disease in STAT6-Deficient Mice Requires Hemopoietic and Nonhemopoietic Cells and Is IFN-γ Dependent

Ostrand‐Rosenberg

Clements

Terabe

et al. 2002

The Journal of Immunology

107

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Mice deficient for the STAT6 gene (STAT6−/− mice) have enhanced immunosurveillance against primary and metastatic tumors. Because STAT6 is a downstream effector of the IL-4R, and IL-13 binds to the type 2 IL-4R, IL-13 has been proposed as an inhibitor that blocks differentiation of tumor-specific CD8+ T cells. Immunity in STAT6−/− mice is unusually effective in that 45–80% of STAT6−/− mice with established, spontaneous metastatic 4T1 mammary carcinoma, whose primary tumors are surgically excised, survive indefinitely, as compared with <10% of STAT+/+ (BALB/c) mice. Surprisingly, STAT6−/− and BALB/c reciprocal bone marrow chimeras do not have increased immunosurveillance, demonstrating that immunity requires STAT6−/− hemopoietic and nonhemopoietic components. Likewise, CD1−/− mice that are NKT deficient and therefore IL-13 deficient also have heightened tumor immunity. However, STAT6−/− and CD1−/− reciprocal bone marrow chimeras do not have increased survival, suggesting that immunity in STAT6−/− and CD1−/− mice is via noncomplementing mechanisms. Metastatic disease is not reduced in BALB/c mice treated with an IL-13 inhibitor, indicating that IL-13 alone is insufficient for negative regulation of 4T1 immunity. Likewise, in vivo depletion of CD4+CD25+ T cells in BALB/c mice does not increase survival, demonstrating that CD4+CD25+ cells do not regulate immunity. Cytokine production and tumor challenges into STAT6−/−IFN-γ−/− mice indicate that IFN-γ is essential for immunity. Therefore, immunosurveillance in STAT6−/− mice facilitates survival against metastatic cancer via an IFN-γ-dependent mechanism involving hemopoietic and nonhemopoietic derived cells, and is not exclusively dependent on counteracting IL-13 or CD4+CD25+ T cells.

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“…This paradigm has been extended to tumor immunity, and investigators have proposed that Th1 cells are the desired CD4 ϩ population because they facilitate differentiation of tumor-specific CD8 ϩ T cells (18,19), which are potent anti-tumor effectors (20). Although the correlation between STAT4 Ϫ/Ϫ and STAT6 Ϫ/Ϫ mice and deficiencies in Th1 and Th2 cells, respectively, is not absolute, we speculated that these mice might provide useful information on the roles of Th1 and Th2 cells in anti-tumor immunity.…”

mentioning

confidence: 99%

Cutting Edge: STAT6-Deficient Mice Have Enhanced Tumor Immunity to Primary and Metastatic Mammary Carcinoma

Ostrand‐Rosenberg

Grusby

Clements

2000

The Journal of Immunology

132

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STAT4 and STAT6 are essential for the development of CD4+ Th1 and Th2 development, respectively. Tumor immunologists have hypothesized that Th1 cells are critical in tumor immunity because they facilitate differentiation of CD8+ T cells, which are potent anti-tumor effectors. We have used STAT4−/− and STAT6−/− mice to test this hypothesis. BALB/c and knockout mice were challenged in the mammary gland with the highly malignant and spontaneously metastatic BALB/c-derived 4T1 mammary carcinoma. Primary tumor growth and metastatic disease are reduced in STAT6−/− mice relative to BALB/c and STAT4−/− mice. Ab depletions demonstrate that the effect is mediated by CD8+ T cells, and immunized STAT6−/− mice have higher levels of 4T1-specific CTL than BALB/c or STAT4−/− mice. Surprisingly, Th1 or Th2 cells are not involved, because CD4 depletion does not diminish the anti-tumor effect. Therefore, deletion of the STAT6 gene facilitates development of potent anti-tumor immunity via a CD4+-independent pathway.

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Th1/Th2 balance in cancer, transplantation and pregnancy

Cited by 36 publications

References 0 publications

Paradoxical Roles of IL-4 in Tumor Immunity

Paradoxical Roles of IL-4 in Tumor Immunity

Resistance to Metastatic Disease in STAT6-Deficient Mice Requires Hemopoietic and Nonhemopoietic Cells and Is IFN-γ Dependent

Cutting Edge: STAT6-Deficient Mice Have Enhanced Tumor Immunity to Primary and Metastatic Mammary Carcinoma

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