This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nakajima, C. Articles by Hamaoka, T. Search for Related Content PubMed PubMed Citation Articles by Nakajima, C. Articles by Hamaoka, T.

A Role of Interferon- (IFN-) in Tumor Immunity

T Cells with the Capacity to Reject Tumor Cells Are Generated But Fail to Migrate to Tumor Sitesin IFN--deficient Mice¹

Department of Oncology, Biomedical Research Center, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871 [C.N., Y.U., M.I., N.Y., T.M., P.G., M.T., S.O., H.F., T.H.], and Department of Pathology, Sumitomo Hospital, Osaka 563-0005 [T.T.], Japan

IFN--deficient (IFN-^-/-) 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-^-/- 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-^-/- mice. Similarly, splenic T cells from interleukin 12-treated CSA1M-bearing IFN-^-/- 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-^-/- mice. These results indicate a critical requirement for IFN- in the process of inducing T-cell migration to tumor sites rather than of generating antitumor protective T cells.

This article has been cited by other articles:

				A. E. Seif, D. M. Barrett, M. Milone, V. I. Brown, S. A. Grupp, and G. S. D. Reid Long-term protection from syngeneic acute lymphoblastic leukemia by CpG ODN-mediated stimulation of innate and adaptive immune responses Blood, September 17, 2009; 114(12): 2459 - 2466. [Abstract] [Full Text] [PDF]

				J. A. Hollenbaugh and R. W. Dutton IFN-{gamma} Regulates Donor CD8 T Cell Expansion, Migration, and Leads to Apoptosis of Cells of a Solid Tumor. J. Immunol., September 1, 2006; 177(5): 3004 - 3011. [Abstract] [Full Text] [PDF]

				T. Ono, M. Harada, A. Yamada, M. Tanaka, Y. Takao, Y. Tanaka, T. Mine, K. Sakamoto, T. Nakashima, and K. Itoh Antitumor Effects of Systemic and Local Immunization with a CTL-Directed Peptide in Combination with a Local Injection of OK-432 Clin. Cancer Res., February 15, 2006; 12(4): 1325 - 1332. [Abstract] [Full Text] [PDF]

				S. Yu, G. C. Sharp, and H. Braley-Mullen Thyrocytes Responding to IFN-{gamma} Are Essential for Development of Lymphocytic Spontaneous Autoimmune Thyroiditis and Inhibition of Thyrocyte Hyperplasia J. Immunol., January 15, 2006; 176(2): 1259 - 1265. [Abstract] [Full Text] [PDF]

				M. Moeller, N. M. Haynes, M. H. Kershaw, J. T. Jackson, M. W. L. Teng, S. E. Street, L. Cerutti, S. M. Jane, J. A. Trapani, M. J. Smyth, et al. Adoptive transfer of gene-engineered CD4+ helper T cells induces potent primary and secondary tumor rejection Blood, November 1, 2005; 106(9): 2995 - 3003. [Abstract] [Full Text] [PDF]

				Q. Li, A. L. Carr, E. J. Donald, J. J. Skitzki, R. Okuyama, L. M. Stoolman, and A. E. Chang Synergistic Effects of IL-12 and IL-18 in Skewing Tumor-Reactive T-Cell Responses Towards a Type 1 Pattern Cancer Res., February 1, 2005; 65(3): 1063 - 1070. [Abstract] [Full Text] [PDF]

				J. Skitzki, R. A. Craig, R. Okuyama, R. N. Knibbs, K. McDonagh, A. E. Chang, and L. M. Stoolman Donor Cell Cycling, Trafficking, and Accumulation during Adoptive Immunotherapy for Murine Lung Metastases Cancer Res., March 15, 2004; 64(6): 2183 - 2191. [Abstract] [Full Text] [PDF]

				K. Chamoto, T. Tsuji, H. Funamoto, A. Kosaka, J. Matsuzaki, T. Sato, H. Abe, K. Fujio, K. Yamamoto, T. Kitamura, et al. Potentiation of Tumor Eradication by Adoptive Immunotherapy with T-cell Receptor Gene-Transduced T-Helper Type 1 Cells Cancer Res., January 1, 2004; 64(1): 386 - 390. [Abstract] [Full Text] [PDF]

				N. M. Haynes, J. A. Trapani, M. W. L. Teng, J. T. Jackson, L. Cerruti, S. M. Jane, M. H. Kershaw, M. J. Smyth, and P. K. Darcy Rejection of Syngeneic Colon Carcinoma by CTLs Expressing Single-Chain Antibody Receptors Codelivering CD28 Costimulation J. Immunol., November 15, 2002; 169(10): 5780 - 5786. [Abstract] [Full Text] [PDF]

				N. M. Haynes, J. A. Trapani, M. W. L. Teng, J. T. Jackson, L. Cerruti, S. M. Jane, M. H. Kershaw, M. J. Smyth, and P. K. Darcy Single-chain antigen recognition receptors that costimulate potent rejection of established experimental tumors Blood, October 16, 2002; 100(9): 3155 - 3163. [Abstract] [Full Text] [PDF]

				J. G. Segal, N. C. Lee, Y. L. Tsung, J. A. Norton, and K. Tsung The Role of IFN-{gamma} in Rejection of Established Tumors by IL-12 : Source of Production and Target Cancer Res., August 15, 2002; 62(16): 4696 - 4703. [Abstract] [Full Text] [PDF]

				R. E. Miller, J. Jones, T. Le, J. Whitmore, N. Boiani, B. Gliniak, and D. H. Lynch 4-1BB-Specific Monoclonal Antibody Promotes the Generation of Tumor-Specific Immune Responses by Direct Activation of CD8 T Cells in a CD40-Dependent Manner J. Immunol., August 15, 2002; 169(4): 1792 - 1800. [Abstract] [Full Text] [PDF]

				R. A. Wilcox, D. B. Flies, H. Wang, K. Tamada, A. J. Johnson, L. R. Pease, M. Rodriguez, Y. Guo, and L. Chen Impaired Infiltration of Tumor-specific Cytolytic T Cells in the Absence of Interferon-{gamma} despite Their Normal Maturation in Lymphoid Organs during CD137 Monoclonal Antibody Therapy Cancer Res., August 1, 2002; 62(15): 4413 - 4418. [Abstract] [Full Text] [PDF]

				S. E.A. Street, J. A. Trapani, D. MacGregor, and M. J. Smyth Suppression of Lymphoma and Epithelial Malignancies Effected by Interferon {gamma} J. Exp. Med., July 1, 2002; 196(1): 129 - 134. [Abstract] [Full Text] [PDF]

				Y. Uekusa, W.-G. Yu, T. Mukai, P. Gao, N. Yamaguchi, M. Murai, K. Matsushima, S. Obika, T. Imanishi, Y. Higashibata, et al. A Pivotal Role for CC Chemokine Receptor 5 in T-Cell Migration to Tumor Sites Induced by Interleukin 12 Treatment in Tumor-bearing Mice Cancer Res., July 1, 2002; 62(13): 3751 - 3758. [Abstract] [Full Text] [PDF]

				T. Hayashi and D. L. Faustman Development of Spontaneous Uterine Tumors in Low Molecular Mass Polypeptide-2 Knockout Mice Cancer Res., January 1, 2002; 62(1): 24 - 27. [Abstract] [Full Text] [PDF]