Dendritic Cell Infiltration and Prognosis of Early Stage Breast Cancer

• Published in: Clinical cancer research Vol. 10; no. 22; pp. 7466 - 7474
• Main Authors: TREILLEUX, Isabelle, BLAY, Jean-Yves, LEBECQUE, Serge, BENDRISS-VERMARE, Nathalie, RAY-COQUARD, Isabelle, BACHELOT, Thomas, GUASTALLA, Jean-Paul, BREMOND, Alain, GODDARD, Sophie, PIN, Jean-Jacques, BARTHELEMY-DUBOIS, Clarisse
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15-11-2004
• Subjects: Adult; Aged; Aged, 80 and over; Antigens, CD; Antigens, Surface - biosynthesis; Antineoplastic agents; Biological and medical sciences; Breast Neoplasms - diagnosis; Breast Neoplasms - pathology; CD3 Complex - biosynthesis; Dendritic Cells - cytology; Dendritic Cells - pathology; Disease Progression; Disease-Free Survival; Female; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; Interleukin-3 Receptor alpha Subunit; Lectins, C-Type - biosynthesis; Lymphatic Metastasis; Mammary gland diseases; Mannose-Binding Lectins - biosynthesis; Medical sciences; Middle Aged; Multivariate Analysis; Pharmacology. Drug treatments; Prognosis; Receptors, Chemokine - biosynthesis; Receptors, Interleukin-3 - biosynthesis; Recurrence; T-Lymphocytes - cytology; Time Factors; Treatment Outcome; Tumors; Mammary gland diseases; Dendritic cell; Prognosis; Antigen presenting cell; Early stage; Infiltration; Breast cancer; Malignant tumor
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-04-0684

Purpose: Although dendritic cells (DC) and T cells can infiltrate primary breast carcinoma, it remains unclear whether the immune
response influences the clinical outcome.
Experimental Design: 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.