Chemokine receptor expression in tumour islets and stroma in non-small cell lung cancer.
BACKGROUND
We have previously demonstrated that tumour islet infiltration by macrophages is associated with extended survival (ES) in NSCLC. We therefore hypothesised that patients with improved survival would have high tumour islet expression of chemokine receptors known to be associated with favourable prognosis in cancer. This study investigated chemokine receptor expression in the tumour islets and stroma in NSCLC.


METHODS
We used immunohistochemistry to identify cells expressing CXCR1, CXCR2, CXCR3, CXCR4, CXCR5 and CCR1 in the tumour islets and stroma in 20 patients with surgically resected NSCLC. Correlations were made with macrophage and mast cell expression.


RESULTS
There was increased expression of CXCR2, CXCR3, and CCR1 in the tumour islets of ES compared with poor survival (PS) patients (p = 0.007, 0.01, and 0.002, respectively). There was an association between 5 year survival and tumour islet CXCR2, CXCR3 and CCR1 density (p = 0.02, 0.003 and <0.001, respectively) as well as stromal CXCR3 density (p = 0.003). There was a positive correlation between macrophage density and CXCR3 expression (rs = 0.520, p = 0.02) and between mast cell density and CXCR3 expression (rs = 0.499, p = 0.03) in the tumour islets.


CONCLUSIONS
Above median expression of CXCR2, CXCR3 and CCR1 in the tumour islets is associated with increased survival in NSCLC, and expression of CXCR3 correlates with increased macrophage and mast cell infiltration in the tumour islets.
Ohri
Chandra M
CM
Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK. cohri@doctors.org.uk
Shikotra
Aarti
A
Green
Ruth H
RH
Waller
David A
DA
Bradding
Peter
P
D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D002633:Chemotaxis; D016009:Chi-Square Distribution; D004847:Epithelial Cells / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008264:Macrophages / Q000276:immunology; D008297:Male; D008407:Mast Cells / Q000276:immunology; D008875:Middle Aged; D054389:Receptors, CCR1 / Q000032:analysis; D054367:Receptors, CXCR3 / Q000032:analysis; D019707:Receptors, Chemokine / Q000032:analysis*; D023063:Receptors, Interleukin-8B / Q000032:analysis; D017154:Stromal Cells / Q000276:immunology* / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation
C515300:CCR1 protein, human; C515187:CXCR3 protein, human; D054389:Receptors, CCR1; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D023063:Receptors, Interleukin-8B