CCL21 is an effective surgical neoadjuvant for treatment of mammary tumors.
In previous studies, the chemokine CCL21 has shown biological activities that include T cell, natural killer (NK) cell, and dendritic cell (DC) chemoattraction. The goal of this study was to determine the effects of administering CCL21 to orthotopic mammary tumors in terms of impact on tumor growth rate, immune cell infiltration of the primary tumor and survival. We found that a single intratumoral administration of CCL21 slowed the growth of orthotopic mammary tumors and increased intratumoral infiltration by T cells, NK cells and DCs. CCL21 intratumoral administration also prolonged the survival of tumor-earing mice. Furthermore, mice that received intratumoral neoadjuvant CCL21 ior to surgical resection of tumors survived significantly longer than control mice. The urviving neoadjuvant CCL21-reated mice, when challenged again with cl-6, had significantly slower rate of tumor growth than challenged control mice. Thus, our ata indicate that CCL21 treatment prior to mammary tumor resection can significantly rolong survival and increase resistance to subsequent tumor challenge. Overall, our indings suggest that intratumoral administration of CCL21 has potential as a neoadjuvant mmunotherapy for breast cancer.
Ashour
Abdelkader E
AE
Eppley Institute, Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska 68198-6805, USA.
Lin
Xuede
X
Wang
Xiaojian
X
Turnquist
Heth R
HR
Burns
Nicole M
NM
Tuli
Amit
A
Sadanandam
Anguraj
A
Suleiman
Khaled
K
Singh
Rakesh K
RK
Talmadge
James E
JE
Solheim
Joyce C
JC
D000818:Animals; D054421:Chemokine CCL21 / Q000008:administration & dosage / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000187:drug effects; D005260:Female; D007694:Killer Cells, Natural / Q000187:drug effects; D016246:Lymphocytes, Tumor-Infiltrating; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy* / Q000276:immunology* / Q000601:surgery; D051379:Mice; D008807:Mice, Inbred BALB C; D020360:Neoadjuvant Therapy / Q000379:methods*; D013601:T-Lymphocytes / Q000187:drug effects
D054421:Chemokine CCL21