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01-09-2011 | Original article

Immunotherapy eradicates metastases with reversible defects in MHC class I expression

Authors: Cristina Garrido, Irene Romero, Enrique Berruguilla, Bárbara Cancela, Ignacio Algarra, Antonia Collado, Angel García-Lora, Federico Garrido

Published in: Cancer Immunology, Immunotherapy | Issue 9/2011

Abstract

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.

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Title: Immunotherapy eradicates metastases with reversible defects in MHC class I expression
Authors: Cristina Garrido
Irene Romero
Enrique Berruguilla
Bárbara Cancela
Ignacio Algarra
Antonia Collado
Angel García-Lora
Federico Garrido
Publication date: 01-09-2011
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 9/2011
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-011-1027-1

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