Interleukin-12 activated CD8+T cells induces apoptosis in breast cancer cells and reduces tumor growth.
During the past two decades, cytokines have emerged as key molecules to modulate innate and adaptive immunity and mediate anti-tumor activity. Although multiple cytokine types are implicated for such anti-tumor activity in several cancer types, it remains largely unknown in breast cancer. In this study, cytokines that are prior known for antitumor activity in different cancer types were examined against breast cancer using a 4T1 cells based xenograft-model. Our results showed Interleukin-12 (IL-12) (500ng/mouse) significantly suppressed the growth of tumors, while other cytokines showed minimal suppression. Subsequent molecular analysis by flow cytometry and immunohistochemistry confirmed the CD8+cells infiltration and Interferon-γ (IFN-γ) production by them in tumor environment. In addition, we observed that IFN-γ production by activated CD8+cells directly induced apoptosis in tumor cells, which together indicate that IL-12 causes CD8+cells to infiltrate and secrete IFN-γ in tumor environment, which induce apoptosis in them and causes tumor growth suppression. Furthermore, we showed that lower dosage of IL-12 and chemotherapy drug tamoxifen combinations enhanced the tumor suppression as opposed to single treatments, and thereby propose an alternate option for high dosage associated effects for both drug and cytokine treatments.
Department of Galactophore, The Third Hospital of Nanchang, Breast Hospital of Jiangxi, 330009, China. Electronic address: yangshixin002@hotmail.com.
Shi-Xin
SX
Yang
Department of Galactophore, The Third Hospital of Nanchang, Breast Hospital of Jiangxi, 330009, China.
Wen-Song
WS
Wei
Department of Galactophore, The Third Hospital of Nanchang, Breast Hospital of Jiangxi, 330009, China.
Qian-Wen
QW
Ouyan
Department of Galactophore, The Third Hospital of Nanchang, Breast Hospital of Jiangxi, 330009, China.
Qi-Hua
QH
Jiang
Department of Galactophore, The Third Hospital of Nanchang, Breast Hospital of Jiangxi, 330009, China.
Yu-Feng
YF
Zou
Department of Galactophore, The Third Hospital of Nanchang, Breast Hospital of Jiangxi, 330009, China.
Wei
W
Qu
Department of Galactophore, The Third Hospital of Nanchang, Breast Hospital of Jiangxi, 330009, China.
Jian-Hong
JH
Tu
Department of Galactophore, The Third Hospital of Nanchang, Breast Hospital of Jiangxi, 330009, China.
Zhi-Bing
ZB
Zhou
Department of Galactophore, The Third Hospital of Nanchang, Breast Hospital of Jiangxi, 330009, China.
Hao-Long
HL
Ding
Department of Galactophore, The Third Hospital of Nanchang, Breast Hospital of Jiangxi, 330009, China.
Chun-Wei
CW
Xie
Department of Galactophore, The Third Hospital of Nanchang, Breast Hospital of Jiangxi, 330009, China.
Qiu-Mo
QM
Lei
Department of Galactophore, The Third Hospital of Nanchang, Breast Hospital of Jiangxi, 330009, China.
Cheng-Ren
CR
Zhong
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D018664:Interleukin-12 / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D047368:Tumor Burden / Q000187:drug effects* / Q000502:physiology
D018664:Interleukin-12
4T1 cells; Breast cancer; CD8(+) cells; Interferon-γ; Interleukin-12