Intratumoral expression of mature human neutrophil peptide-1 mediates antitumor immunity in mice.
OBJECTIVE
Human neutrophil peptides (HNP1-3), small molecular antimicrobial peptides, are expressed within tumors and associated with tumor necrosis and inhibition of angiogenesis. Recent investigations have suggested that HNP1-3 are likely to be involved in the host immune responses to tumors.


METHODS
We used recombinant pSec-HNP1, which expresses a secretable form of HNP1, to obtain expression of HNP1 in the tumor milieu in immunocompetent mice to explore the possible roles of HNP1 in tumor immunity. The antitumor effects were investigated in established CT26 colon cancer and 4T1 breast cancer models.


RESULTS
HNP1-mediated chemotactic and activating effects on immature dendritic cells were detected both in vitro and in vivo. Intratumoral expression of HNP1 resulted in not only significant tumor growth inhibition but also increased CTL infiltration within tumors. Adoptive transfer of splenocytes and a (51)Cr release assay revealed specific cellular immune responses. Furthermore, increased antibodies were also found in sera from pSec-HNP1-treated mice supporting specific humoral immune responses. Increased apoptosis and decreased angiogenesis were also shown in treated tumors.


CONCLUSIONS
These findings indicate that HNP1 can exert multiple antitumor effects through different mechanisms; more importantly, HNP1 mediates host immune responses to tumors in situ through the recruitment and subsequent activation of immature dendritic cells and thus shows promising potential in cancer therapy.
Wang
Yong-Sheng
YS
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and Department of Gynecology and Obstetrics, Second West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, People's Republic of China. wangys@scu.edu.cn
Li
Dan
D
Shi
Hua-Shan
HS
Wen
Yan-Jun
YJ
Yang
Li
L
Xu
Ning
N
Chen
Xian-Cheng
XC
Chen
Xiang
X
Chen
Ping
P
Li
Jiong
J
Deng
Hong-Xin
HX
Wang
Chun-Ting
CT
Xie
Gang
G
Huang
Shan
S
Mao
Yong-Qiu
YQ
Chen
Li-Juan
LJ
Zhao
Xia
X
Wei
Yu-Quan
YQ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000737:chemistry / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D014162:Transfection; D023084:alpha-Defensins / Q000096:biosynthesis*
D000970:Antineoplastic Agents; D016207:Cytokines; D023084:alpha-Defensins; C406413:human neutrophil peptide 1