title: T lymphocytes restrain spontaneous metastases in permanent dormancy.
abstract: Tumor dormancy is a clinical phenomenon related to immune equilibrium during cancer immunoediting. The mechanisms involved in dormant metastases are poorly understood due to the lack of preclinical models. Here, we present a nontransgenic mouse model in which spontaneous metastases remain in permanent immunomediated dormancy with no additional antitumor treatment. After the injection of a GR9-B11 mouse fibrosarcoma clone into syngeneic BALB/c mice, all animals remained free of spontaneous metastases at the experimental endpoints (3-8 months) but also as long as 24 months after tumor cell injection. Strikingly, when tumor-bearing mice were immunodepleted of T lymphocytes or asialo GM1-positive cells, the restraint on dormant disseminated metastatic cells was relieved and lung metastases progressed. Immunostimulation was documented at both local and systemic levels, with results supporting the evidence that the immune system was able to restrain spontaneous metastases in permanent dormancy. Notably, the GR9-B11 tumor clone did not express MHC class I molecules on the cell surface, yet all metastases in immunodepleted mice were MHC class I-positive. This model system may be valuable for more in-depth analyses of metastatic dormancy, offering new opportunities for immunotherapeutic management of metastatic disease.
authors: Authors' Affiliations: Dept. Analisis Clinicos e Inmunologia, UGC Laboratorio Clínico; Unidad de Investigación, Hospital Universitario Virgen de las Nieves, Granada; Departamento de Bioquímica, Biología Molecular e Inmunología III, Universidad de Granada, Granada; and Departamento de Ciencias de la Salud, Universidad de Jaén, Jaén, Spain.
authors: Irene
authors: I
authors: Romero
authors: Cristina
authors: C
authors: Garrido
authors: Ignacio
authors: I
authors: Algarra
authors: Antonia
authors: A
authors: Collado
authors: Federico
authors: F
authors: Garrido
authors: Angel M
authors: AM
authors: Garcia-Lora
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005354:Fibrosarcoma / Q000276:immunology / Q000473:pathology; D005677:G(M1) Ganglioside / Q000502:physiology; D006183:H-2 Antigens / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D006183:H-2 Antigens; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside