Carcinoma-Derived Interleukin-8 Disorients Dendritic Cell Migration Without Impairing T-Cell Stimulation

被引：34

作者：

Alfaro, Carlos ^{[1
]}

Suarez, Natalia ^{[1
,2
]}

Martinez-Forero, Ivan ^{[1
]}

Palazon, Asis ^{[1
]}

Rouzaut, Ana ^{[1
]}

Solano, Sarai ^{[1
]}

Feijoo, Esperanza ^{[1
]}

Gurpide, Alfonso ^{[3
]}

Bolanos, Elixabet ^{[1
,3
]}

Erro, Lorena ^{[1
]}

Dubrot, Juan ^{[1
]}

Hervas-Stubbs, Sandra ^{[1
]}

Gonzalez, Alvaro ^{[2
]}

Luis Perez-Gracia, Jose ^{[3
]}

Melero, Ignacio ^{[1
,3
]}

机构：

[1] CIMA, Gene Therapy & Hepatol Div, Pamplona, Spain

[2] Univ Navarra Clin, Dept Biochem, Pamplona, Spain

[3] Univ Navarra Clin, Dept Med Oncol, Pamplona, Spain

来源：

PLOS ONE | 2011年 / 6卷 / 03期

关键词：

INTRATUMORAL INJECTION; TUMOR MICROENVIRONMENT; CANCER-IMMUNOTHERAPY; ANTITUMOR IMMUNITY; MELANOMA PATIENTS; GROWTH-FACTOR; CHEMOKINES; RECEPTOR; INFLAMMATION; EXPRESSION;

D O I：

10.1371/journal.pone.0017922

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Background: Interleukin-8 (IL-8, CXCL8) is readily produced by human malignant cells. Dendritic cells (DC) both produce IL-8 and express the IL-8 functional receptors CXCR1 and CXCR2. Most human colon carcinomas produce IL-8. IL-8 importance in malignancies has been ascribed to angiogeneis promotion. Principal Findings: IL-8 effects on human monocyte-derived DC biology were explored upon DC exposure to recombinant IL-8 and with the help of an IL-8 neutralizing mAb. In vivo experiments were performed in immunodeficient mice xenografted with IL-8-producing human colon carcinomas and comparatively with cell lines that do not produce IL-8. Allogenic T lymphocyte stimulation by DC was explored under the influence of IL-8. DC and neutrophil chemotaxis were measured by transwell-migration assays. Sera from tumor-xenografted mice contained increasing concentrations of IL-8 as the tumors progress. IL-8 production by carcinoma cells can be modulated by low doses of cyclophosphamide at the transcription level. If human DC are injected into HT29 or CaCo2 xenografted tumors, DC are retained intratumorally in an IL-8-dependent fashion. However, IL-8 did not modify the ability of DC to stimulate T cells. Interestingly, pre-exposure of DC to IL-8 desensitizes such cells for IL-8-mediated in vitro or in vivo chemoattraction. Thereby DC become disoriented to subsequently follow IL-8 chemotactic gradients towards malignant or inflamed tissue. Conclusions: IL-8 as produced by carcinoma cells changes DC migration cues, without directly interfering with DC-mediated T-cell stimulation.

引用

页数：14

共 58 条

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