Immunotherapy eradicates metastases with reversible defects in MHC class I expression

• Published in: Cancer Immunology, Immunotherapy Immunotherapy, 2011-09, Vol.60 (9), p.1257-1268
• Main Authors: Garrido, Cristina, Romero, Irene, Berruguilla, Enrique, Cancela, Bárbara, Algarra, Ignacio, Collado, Antonia, García-Lora, Angel, Garrido, Federico
• Format: Article
• Language: English
• Subjects: Animals; Antigens; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Biological and medical sciences; Cancer Research; Cancer therapies; Cell Line, Tumor; Chemotherapy; Combined Modality Therapy; Docetaxel; Fibrosarcoma - immunology; Fibrosarcoma - secondary; Fibrosarcoma - therapy; Histocompatibility Antigens Class I - immunology; Humans; Immune system; Immunology; Immunotherapy; Immunotherapy, Adoptive - methods; Laboratory animals; Leukocytes; Lung Neoplasms - immunology; Lung Neoplasms - secondary; Lung Neoplasms - therapy; Lymphatic Metastasis; Lymphatic system; Male; Medical sciences; Medicine; Medicine & Public Health; Melanoma; Metastasis; Mice; Mice, Inbred BALB C; Oncology; Original; Original Article; Pharmacology. Drug treatments; Proteins; Proteoglycans - therapeutic use; Taxoids - therapeutic use; Tumors; Vaccines
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-011-1027-1

Tumor or metastatic cells lose MHC class I (MHC-I) expression during cancer progression as an escape mechanism from immune surveillance. These defects in MHC-I may be reversible by cytokines or different agents (soft lesions) or irreversible due to structural defects (hard lesions). The nature of these MHC-I alterations might determine the success or failure of immunotherapy treatments. In this study, we have used an MHC-I-positive murine fibrosarcoma tumor clone, GR9-A7, which generates multiple lung and lymph node metastases with reversible MHC-I alterations after treatment with IFN-γ. Four different antitumor treatments were carried out after primary tumor excision to determine their capacity to inhibit spontaneous metastatic colonization of the GR9-A7 tumor clone. We found that 2 different immunotherapy protocols (CpG plus autologous irradiated-GR9-A7 cells and protein-bound polysaccharide K (PSK) and 1 chemoimmunotherapy (docetaxel plus PSK) induced eradication of metastases. In contrast, chemotherapy with docetaxel alone produced only partial reduction in the number of metastases. Flow cytometric analysis of lymphocyte populations showed an immunosuppression in GR9-A7 tumor-bearing host, which could be reverted by immunotherapy treatments. Our results suggest that irreversible or reversible MHC-I alterations in tumor target cells may determine its progression or regression independently of the type of immunotherapy used.