A role of interferon-gamma (IFN-gamma) in tumor immunity: T cells with the capacity to reject tumor cells are generated but fail to migrate to tumor sites in IFN-gamma-deficient mice.
IFN-gamma-deficient (IFN-gamma-/-) mice induce potent in vitro immune responses such as anti-allo mixed lymphocyte reaction and CTL responses, whereas they often fail to exhibit in vivo immunity. Here, we investigated whether there exists a defect in tumor rejection responses and if so, which process of responses is impaired. IFN-gamma-/- and wild-type (WT) BALB/c mice were immunized with attenuated syngeneic CSA1M tumor cells. The capacity of T cells to mediate tumor protection was examined in Winn assays to assess the growth of tumor cells admixed with tumor-sensitized T cells. Splenic T cells from both groups of mice exhibited comparable levels of tumor-neutralizing activity. When portions of immunized mice were directly challenged with viable tumor cells, tumor rejection was induced only in WT mice. CD4(+) and CD8(+) T-cell infiltration were observed at the site of tumor challenge in WT mice, whereas such a T-cell infiltration did not occur in IFN-gamma-/- mice. Similarly, splenic T cells from interleukin 12-treated CSA1M-bearing IFN-gamma-/- and WT mice neutralized tumor cells at comparable efficacies in Winn assays. However, the migration of these T cells to tumor masses and the resultant interleukin 12-induced tumor regression took place in WT mice, but neither intratumoral T-cell infiltration nor tumor regression occurred in IFN-gamma-/- mice. These results indicate a critical requirement for IFN-gamma in the process of inducing T-cell migration to tumor sites rather than of generating antitumor protective T cells.
Nakajima
C
C
Department of Oncology, Biomedical Research Center, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
Uekusa
Y
Y
Iwasaki
M
M
Yamaguchi
N
N
Mukai
T
T
Gao
P
P
Tomura
M
M
Ono
S
S
Tsujimura
T
T
Fujiwara
H
H
Hamaoka
T
T
D000818:Animals; D002465:Cell Movement / Q000276:immunology*; D005354:Fibrosarcoma / Q000276:immunology*; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D018664:Interleukin-12 / Q000276:immunology / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D018664:Interleukin-12; D007371:Interferon-gamma