Dendritic cell infiltration and prognosis of early stage breast cancer.
OBJECTIVE
Although dendritic cells (DC) and T cells can infiltrate primary breast carcinoma, it remains unclear whether the immune response influences the clinical outcome.


METHODS
T lymphocytes and DC infiltration within primary tumors was investigated in 152 patients with invasive nonmetastatic breast cancer. CD1a, CD3, CD68, CD123, CD207/Langerin, and CD208/DC-LAMP expression was assessed with semiquantitative immunohistochemical analysis. Expression of chemokines involved in DC migration (MIP-3a/CCL20, MIP-3b/CCL19, and 6Ckine/CCL21) was also examined. The correlation between these markers and the characteristics of the tumors, as well as relapse-free and overall survival was analyzed. Significant prognostic parameters were then tested in a validation series.


RESULTS
Infiltration by immature CD207/Langerin+ DC was found in a third of the cancers and did not correlate with clinicopathological data. Presence of mature CD208/DC-LAMP+ DC (56%) and CD3+ T cells (82%) strongly correlated with lymph node involvement and tumor grade. Among the chemokines analyzed, only the presence of MIP-3b/CCL19 in 57% of the tumors correlated with prolonged overall survival. CD123+ plasmacytoid DC (pDC) infiltrated 13% of the primary tumors. Their presence was strongly associated with shorter overall survival (93% versus 58% at 60 months) and relapse-free survival (90% versus 37% at 60 months) and was found to be an independent prognostic factor for overall survival and relapse-free survival and confirmed in an independent validation series of 103 patients.


CONCLUSIONS
Infiltration by pDC of primary localized breast tumor correlates with an adverse outcome, suggesting their contribution in the progression of breast cancer.
Treilleux
Isabelle
I
Departments of Pathology, Medicine, Surgery, Radiotherapy and Radiology, and Equipe Cytokines et Cancers--INSERM U590 Lyon, France.
Blay
Jean-Yves
JY
Bendriss-Vermare
Nathalie
N
Ray-Coquard
Isabelle
I
Bachelot
Thomas
T
Guastalla
Jean-Paul
JP
Bremond
Alain
A
Goddard
Sophie
S
Pin
Jean-Jacques
JJ
Barthelemy-Dubois
Clarisse
C
Lebecque
Serge
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD; D000954:Antigens, Surface / Q000096:biosynthesis; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000473:pathology*; D017252:CD3 Complex / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology* / Q000473:pathology*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053650:Interleukin-3 Receptor alpha Subunit; D037181:Lectins, C-Type / Q000096:biosynthesis; D008207:Lymphatic Metastasis; D037241:Mannose-Binding Lectins / Q000096:biosynthesis; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D019707:Receptors, Chemokine / Q000096:biosynthesis; D016185:Receptors, Interleukin-3 / Q000096:biosynthesis; D012008:Recurrence; D013601:T-Lymphocytes / Q000166:cytology; D013997:Time Factors; D016896:Treatment Outcome
D015703:Antigens, CD; D000954:Antigens, Surface; C121916:CD207 protein, human; D017252:CD3 Complex; C115022:IL3RA protein, human; D053650:Interleukin-3 Receptor alpha Subunit; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D019707:Receptors, Chemokine; D016185:Receptors, Interleukin-3