PMID- 10805368
OWN - NLM
STAT- MEDLINE
DCOM- 20000822
LR  - 20181130
IS  - 1079-9907 (Print)
IS  - 1079-9907 (Linking)
VI  - 20
IP  - 4
DP  - 2000 Apr
TI  - Regression of engineered tumor cells secreting cytokines is related to a shift in 
      host cytokine profile from type 2 to type 1.
PG  - 349-54
AB  - The precise role of the endogenous immune response in modulating cancer 
      development remains unclear. In this study, three mouse tumor cell lines were 
      used to elucidate the immune mechanisms for tumor regression versus tumor growth. 
      These cell lines were (1) the poorly immunogenic VKCK cell line and (2) its two 
      derived cell lines VKCK/RM4-tumor necrosis factor-alpha (TNF-alpha) and 
      VKCK/RM4-interferon-gamma (IFN-gamma) engineered to secrete TNF-alpha and 
      IFN-gamma, respectively. Our data showed that VKCK tumors grew aggressively in 
      syngeneic BALB/c mice, and vaccination of irradiated VKCK cells failed to protect 
      the mice from a subsequent challenge with the same tumor. In contrast, engineered 
      VKCK tumor cells lost their tumorigenicity, and vaccination of engineered VKCK 
      cells induced a protective immunity against VKCK cells that was mediated with 
      VKCK-specific CD8+T cells. Susceptible mice developed a Th2-dominant response, 
      whereas resistant mice developed a Th1-dominant response to VKCK. The T cell 
      proliferative response and cytolytic activity against VKCK developed in both 
      resistant and susceptible mice, but in the susceptible mice, these responses were 
      much weaker compared with those in the resistant mice. Our results indicate that 
      regression of tumor cells engineered to secrete cytokines TNF-alpha and IFN-gamma 
      is related to a shift from a host type 2 to a type 1 cytokine profile. Our 
      results further suggest that the failure of unmodified VKCK to generate 
      efficacious T cells is not due to an inability to recognize tumor antigens but, 
      rather, to the nature and magnitude of the antitumor immune response that 
      develops. A better understanding of the mechanisms by which tumor cells modulate 
      the host immune system may result in newer approaches for manipulating host-tumor 
      interactions that favor the development of a protective antitumor immune 
      response.
FAU - Xiang, J
AU  - Xiang J
AD  - Department of Microbiology, College of Medicine, University of Saskatchewan, 
      Saskatoon, Canada. jxiang@scf.sk.ca
FAU - Moyana, T
AU  - Moyana T
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Interferon Cytokine Res
JT  - Journal of interferon & cytokine research : the official journal of the 
      International Society for Interferon and Cytokine Research
JID - 9507088
RN  - 0 (Cytokines)
RN  - 0 (Growth Inhibitors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Cell Division/genetics/immunology
MH  - Cytokines/biosynthesis/*metabolism/physiology
MH  - Female
MH  - Genetic Vectors/chemical synthesis/*metabolism
MH  - Growth Inhibitors/metabolism/physiology
MH  - Interferon-gamma/biosynthesis/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Remission Induction
MH  - Th1 Cells/immunology/*metabolism
MH  - Th2 Cells/immunology/*metabolism
MH  - Tumor Cells, Cultured/*metabolism/*pathology
MH  - Tumor Necrosis Factor-alpha/biosynthesis/metabolism
EDAT- 2000/05/11 09:00
MHDA- 2000/08/29 11:01
CRDT- 2000/05/11 09:00
PHST- 2000/05/11 09:00 [pubmed]
PHST- 2000/08/29 11:01 [medline]
PHST- 2000/05/11 09:00 [entrez]
AID - 10.1089/107999000312270 [doi]
PST - ppublish
SO  - J Interferon Cytokine Res. 2000 Apr;20(4):349-54. doi: 10.1089/107999000312270.