immunology-2018-posters-abstracts

Immunology 2018

J u l y 0 5 - 0 7 , 2 0 1 8

V i e n n a , A u s t r i a

Page 94

Journal of Clinical Immunology and Allergy

ISSN 2471-304X

1 5

t h

I n t e r n a t i o n a l C o n f e r e n c e o n

Immunology

he cytokine thymic stromal lymphopoietin (TSLP) has been implicated in controlling various human cancer developments

through regulating type-2 inflammation via T cells. However, it is still largely unknown the role of TSLP in other cell types

within tumours since TSLP receptor (TSLPR) is widely expressed on many cell types, including hematopoietic cells and epithelial

cells under inflammatory conditions. We found that both human and mouse breast tumour cells express functional TSLPR and

TSLP signalling is important to maintain their survival through inducing Bcl-2

in vitro

. By using murine metastatic breast tumour

models we found the most important TSLP source for maintaining breast tumour cell survival

in vivo

is not derived from tumour

cells but rather from myeloid cells. Furthermore, tumour cell-derived IL-1a is important to increase TSLP expression in myeloid

cells. Blocking TSLP systemically after tumour development has reduced primary tumour size in a spontaneous mouse breast

cancer model. Constitutive expression of TSLP in lungs of mice that mimicked human asthma enhanced tumour cell survival in

lungs that further led to more lung metastases and TSLP blockage only in lungs reduced tumour metastases. Besides tumour

cells, we discovered that TSLP signalling in Ly6Chi monocytes is also crucial for promoting tumour progression by regulating

monocyte suppressor functions and their ability to differentiate into tumour associated macrophages. Our work is the first to

show a tumour-myeloid cell axis, mediated through IL-1a and TSLP, to promote tumour cell survival. We also provided another

novel mechanism of the requirement of TSLP signalling in regulating the pro-tumour functions in Ly6Chi monocytes. These

studies define a novel TSLP-mediated crosstalk between tumour-infiltrating myeloid cells and tumour cells and provide an

effective therapeutic intervention in metastatic breast cancer.

Thymic stromal lymphopoietin promotes interplay

between tumour cells and myeloid cells to regulate

breast tumour progression

Emma L Kuan and Steven F Ziegler

Benaroya Research Institute, USA

Insights Allergy Asthma Bronchitis 2018, Volume: 4

DOI: 10.21767/2471-304X-C1-003