Genome-wide analysis of molecular changes in IL-12-induced control of mammary carcinoma via IFN-γ-independent mechanisms

被引:25
作者
Shi, XY [1 ]
Cao, SJ [1 ]
Mitsuhashi, M [1 ]
Xiang, ZY [1 ]
Ma, XJ [1 ]
机构
[1] Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10021 USA
关键词
D O I
10.4049/jimmunol.172.7.4111
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
IL-12 is a major activator of tumor-killing NK cells and CTL. IFN-gamma mediates most of the well-known immunological activities of IL-12. In this study, we report IFN-gamma-independent activities induced by therapeutic application of rIL-12 in restricting tumor growth and metastasis in the 4T1 murine mammary carcinoma model. IFN-gamma-deficient mice carrying 4T1 tumor exhibit no gross defect in the number of tumor-infiltrating lymphocytes but have exaggerated angiogenesis in the tumor. Administration of IL-12 is able to constrict blood vessels in the tumor in the absence of IFN-gamma, and retains certain therapeutic efficacy even when applied late during tumor progression. IL-12 exposure in vivo does not irreversibly alter the immunogenicity of the tumor. Finally, global gene expression analysis of primary tumors reveals IL-12-induced molecular patterns and changes, implicating a number of novel genes potentially important for IFN-gamma-independent immune responses against the tumor, for IL-12-mediated antiproliferation, antimetastasis, and antiangiogenesis activities.
引用
收藏
页码:4111 / 4122
页数:12
相关论文
共 54 条
[1]   Phase 1 study of interleukin-12 in combination with rituximab in patients with B-cell non-Hodgkin lymphoma [J].
Ansell, SM ;
Witzig, TE ;
Kurtin, PJ ;
Sloan, JA ;
Jelinek, DF ;
Howell, KG ;
Markovic, SN ;
Habermann, TM ;
Klee, GG ;
Atherton, PJ ;
Erlichman, C .
BLOOD, 2002, 99 (01) :67-74
[2]   Interferon-independent, human immunodeficiency virus type 1 gp120-mediated induction of CXCL10/IP-10 gene expression by astrocytes in vivo and in vitro [J].
Asensio, VC ;
Maier, J ;
Milner, R ;
Boztug, K ;
Kincaid, C ;
Moulard, M ;
Phillipson, C ;
Lindsley, K ;
Krucker, T ;
Fox, HS ;
Campbell, IL .
JOURNAL OF VIROLOGY, 2001, 75 (15) :7067-7077
[3]  
ASLAKSON CJ, 1992, CANCER RES, V52, P1399
[4]  
Bodey B, 2001, IN VIVO, V15, P175
[5]   Characterization of mouse ALCAM (CD166): The CD6-binding domain is conserved in different homologs and mediates cross-species binding [J].
Bowen, MA ;
Bajorath, J ;
DEgidio, M ;
Whitney, GS ;
Palmer, D ;
Kobarg, J ;
Starling, GC ;
Siadak, AW ;
Aruffo, A .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1997, 27 (06) :1469-1478
[6]   MHC ANTIGENS AND CANCER - IMPLICATIONS FOR T-CELL SURVEILLANCE [J].
BROWNING, MJ ;
BODMER, WF .
CURRENT OPINION IN IMMUNOLOGY, 1992, 4 (05) :613-618
[7]   THE ROLE OF INDOLEAMINE 2,3-DIOXYGENASE IN THE ANTITUMOR-ACTIVITY OF HUMAN INTERFERON-GAMMA IN-VIVO [J].
BURKE, F ;
KNOWLES, RG ;
EAST, N ;
BALKWILL, FR .
INTERNATIONAL JOURNAL OF CANCER, 1995, 60 (01) :115-122
[8]   CANCER - A BIOLOGICAL APPROACH .3. VIRUSES ASSOCIATED WITH NEOPLASTIC CONDITIONS [J].
BURNET, M .
BMJ-BRITISH MEDICAL JOURNAL, 1957, 1 (APR13) :841-846
[9]   COSTIMULATION OF ANTITUMOR IMMUNITY BY THE B7 COUNTERRECEPTOR FOR THE LYMPHOCYTE-T MOLECULES CD28 AND CTLA-4 [J].
CHEN, LP ;
ASHE, S ;
BRADY, WA ;
HELLSTROM, I ;
HELLSTROM, KE ;
LEDBETTER, JA ;
MCGOWAN, P ;
LINSLEY, PS .
CELL, 1992, 71 (07) :1093-1102
[10]   Interleukin-12 in anti-tumor immunity and immunotherapy [J].
Colombo, MP ;
Trinchieri, G .
CYTOKINE & GROWTH FACTOR REVIEWS, 2002, 13 (02) :155-168