| First Author | Street SE | Year | 2001 |
| Journal | Blood | Volume | 97 |
| Issue | 1 | Pages | 192-7 |
| PubMed ID | 11133760 | Mgi Jnum | J:68550 |
| Mgi Id | MGI:1932832 | Doi | 10.1182/blood.v97.1.192 |
| Citation | Street SE, et al. (2001) Perforin and interferon-gamma activities independently control tumor initiation, growth, and metastasis. Blood 97(1):192-7 |
| abstractText | Perforin (pfp) and interferon-gamma (IFN-gamma) together in C57BL/6 (B6) and BALB/c mouse strains provided optimal protection in 3 separate tumor models controlled by innate immunity. Using experimental (B6, RM-1 prostate carcinoma) and spontaneous (BALB/c, DA3 mammary carcinoma) models of metastatic cancer, mice deficient in both pfp and IFN-gamma were significantly less proficient than pfp- or IFN-gamma-deficient mice in preventing metastasis of tumor cells to the lung. Pfp and IFN-gamma-deficient mice were as susceptible as mice depleted of natural killer (NK) cells in both tumor metastasis models, and IFN-gamma appeared to play an early role in protection from metastasis. Previous experiments in a model of fibrosarcoma induced by the chemical carcinogen methylcholanthrene indicated an important role for NK1.1(+) T cells. Herein, both pfp and IFN-gamma played critical and independent roles in providing the host with protection equivalent to that mediated by NK1.1(+) T cells. Further analysis demonstrated that IFN-gamma, but not pfp, controlled the growth rate of sarcomas arising in these mice. Thus, this is the first study to demonstrate that host IFN-gamma and direct cytotoxicity mediated by cytotoxic lymphocytes expressing pfp independently contribute antitumor effector functions that together control the initiation, growth, and spread of tumors in mice. |
