Thymic Stromal Lymphopoietin Is a Key Mediator of Breast Cancer Progression

Olkhanud, Purevdorj B.; Rochman, Yrina; Bodogai, Monica; Malchinkhuu, Enkhzol; Wejksza, Katarzyna; Xu, Mai; Gress, Ronald E.; Hesdorffer, Charles; Leonard, Warren J.; Biragyn, Arya

doi:10.4049/jimmunol.1100463

Cited by 102 publications

(137 citation statements)

References 33 publications

(67 reference statements)

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“…The suppression of inflammation with the corticosteroid budesonide decreased CD4 + T cell recruitment and metastasis to the lung. Another study concurred with these findings in that activated CD4 + T cells from thymic stromal lymphopoietin-induced airway allergic inflammation resulted in increased tumor growth and lung metastasis [42]. It is well established that macrophages are one of the leukocyte subpopulations that contribute to enhanced tumor growth and metastasis.…”

Section: Allergic Pulmonary Inflammation and Cancersupporting

confidence: 72%

YKL-40/CHI3L1 drives inflammation on the road of tumor progression

Libreros

Iragavarapu-Charyulu

2015

Journal of Leukocyte Biology

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Inflammation plays a vital role at different stages of tumor progression. The development of tumors is affected by inflammatory mediators produced by the tumor and the host. YKL-40/chitinase-3-like-1 protein is often upregulated in inflammation-associated diseases. With the use of chronic inflammatory disease systems, we describe the role of YKL-40/chitinase-3-like-1 protein in enhancing the inflammatory response and its implications in tumorigenesis. We also discuss how pre-existing inflammation enhances tumor growth and metastasis. In this mini-review, we highlight the effect of YKL-40/ chitinase-3-like-1 protein-associated inflammation in promoting tumor progression. J. Leukoc. Biol. 98: 931-936;

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Section: Allergic Pulmonary Inflammation and Cancersupporting

confidence: 72%

YKL-40/CHI3L1 drives inflammation on the road of tumor progression

Libreros

Iragavarapu-Charyulu

2015

Journal of Leukocyte Biology

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“…Unlike observations seen by this study, our observations may have occurred due to the preexisting Th-2 skewed phenotype associated with the 4T1 tumor model. 45 This phenotype may have exacerbated the anaphylactic response to foreign antibodies. Additionally, it has been shown that both Th1 and Th2 responses can stimulate IgG1 production and that a switch from Th2 to Th1 can occur and suppress IgE responses; this can also occur in an organ specific manner if mixed Th1/Th2 responses occur.…”

Section: Discussionmentioning

confidence: 99%

Repeated PD-1/PD-L1 monoclonal antibody administration induces fatal xenogeneic hypersensitivity reactions in a murine model of breast cancer

et al. 2015

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Monoclonal antibodies (mAbs) targeting coinhibitory molecules such as PD-1, PD-L1 and CTLA-4 are increasingly used as targets of therapeutic intervention against cancer. While these targets have led to a critical paradigm shift in treatments for cancer, these approaches are also plagued with limitations owing to cancer immune evasion mechanisms and adverse toxicities associated with continuous treatment. It has been difficult to reproduce and develop interventions to these limitations preclinically due to poor reagent efficacy and reagent xenogenecity not seen in human trials. In this study, we investigated adverse effects of repeated administration of PD-1 and PD-L1 mAbs in the murine 4T1 mammary carcinoma model. We observed rapid and fatal hypersensitivity reactions in tumor bearing mice within 30-60 min after 4-5 administrations of PD-L1 or PD-1 mAb but not CTLA-4 antibody treatment. These events occurred only in mice bearing the highly inflammatory 4T1 tumor and did not occur in mice bearing noninflammatory tumors. We observed that mortality was associated with systemic accumulation of IgG1 antibodies, antibodies specific to the PD-1 mAb, and accumulation of Gr-1 high neutrophils in lungs which have been implicated in the IgG mediated pathway of anaphylaxis. Anti-PD-1 associated toxicities were alleviated when PD-1 blockade was combined with the therapeutic HSP90 inhibitor, ganetespib, which impaired immune responses toward the xenogeneic PD-1 mAb. This study highlights a previously uncharacterized fatal hypersensitivity exacerbated by the PD-1/PD-L1 axis in the broadly used 4T1 tumor model as well as an interesting relationship between this particular class of checkpoint blockade and tumor-dependent immunomodulation.

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“…8,[10][11][12] The hypothesis of an implication of TSLP in the tumor microenvironment stemmed from earlier studies in breast and pancreatic cancer, both in humans and in mice. [13][14][15][16] TSLP expression was associated in these studies with the presence of a Th2-biased inflammatory response, characterized by the expression in T cells of the transcription factor GATA-3, and the production of IL-4, IL-5, IL-13, and TNF. Because a Th2 response has been associated with a poor prognosis, 17,18 TSLP was proposed to be associated with tumor progression and to indicate a bad prognosis of the tumor.…”

Section: Introductionmentioning

confidence: 76%

Ligand–receptor dissociated expression explains high TSLP without prognostic impact in human primary head and neck squamous cell carcinoma

et al. 2016

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Thymic stromal lymphopoietin (TSLP) is an interleukin (IL)-7-like cytokine expressed by epithelial cells during allergic inflammation, and activating dendritic cells (DC). Its expression and functional role in cancer remain controversial. We conducted retrospective (n D 89), and prospective studies including patients with untreated primary head and neck squamous cell carcinoma (HNSCC). We found that TSLP was overexpressed by HNSCC tumor cells, and associated with a highly differentiated status. However, no significant difference in overall and recurrence-free survival was found between patients bearing a tumor with high and low TSLP levels, respectively. Surprisingly, there was no significant association between the levels of TSLP expression, and the number of tumor-infiltrating mature DCLAMP C DC. In order to explain the apparent lack of TSLP-induced DC activation, we performed phenotypic and functional experiments on freshly resected tumors. Tumor-infiltrating immune cells, including DC, did not express the TSLP receptor heterodimer (TSLPR chain, IL-7Ralpha chain). Furthermore, freshly sorted blood CD11c C DC from healthy donors cultured with tumor-conditioned supernatant exhibited an activated profile, but this was not affected by an anti-TSLP blocking antibody, suggesting a DC activation pathway independent of tumor-derived TSLP. Overall, our results demonstrate that TSLP is overexpressed in HNSCC but its function is hampered by the lack of TSLPR-expressing cells in the tumor microenvironment. Such a dissociated ligand-receptor expression may impact intercellular communication in other immune activation pathways, and tumor types.Abbreviations: DC, dendritic cells; HNSCC, head and neck squamous cell carcinoma; TSLP, thymic stromal lymphopoeitin KEYWORDS Cytokines; dendritic cells; head and neck squamous cell carcinoma; thymic stromal lymphopoietin; tumor microenvironment

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Thymic Stromal Lymphopoietin Is a Key Mediator of Breast Cancer Progression

Cited by 102 publications

References 33 publications

YKL-40/CHI3L1 drives inflammation on the road of tumor progression

YKL-40/CHI3L1 drives inflammation on the road of tumor progression

Repeated PD-1/PD-L1 monoclonal antibody administration induces fatal xenogeneic hypersensitivity reactions in a murine model of breast cancer

Ligand–receptor dissociated expression explains high TSLP without prognostic impact in human primary head and neck squamous cell carcinoma

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