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.
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
Yong-Sheng
YS
Wang
Dan
D
Li
Hua-Shan
HS
Shi
Yan-Jun
YJ
Wen
Li
L
Yang
Ning
N
Xu
Xian-Cheng
XC
Chen
Xiang
X
Chen
Ping
P
Chen
Jiong
J
Li
Hong-Xin
HX
Deng
Chun-Ting
CT
Wang
Gang
G
Xie
Shan
S
Huang
Yong-Qiu
YQ
Mao
Li-Juan
LJ
Chen
Xia
X
Zhao
Yu-Quan
YQ
Wei
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