Resection of Solid Tumors Reverses T Cell Defects and Restores Protective Immunity
Autor: | Silvia Salvadori, Giorgio P. Martinelli, Karen Zier |
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Rok vydání: | 2000 |
Předmět: |
CD4-Positive T-Lymphocytes
Adoptive cell transfer Pathology medicine.medical_specialty Fibrosarcoma T cell medicine.medical_treatment Immunology Spleen CD8-Positive T-Lymphocytes Biology Immunophenotyping Mice Immune system T-Lymphocyte Subsets Immunity Tumor Cells Cultured medicine Animals Immunology and Allergy Immunity Cellular Mice Inbred BALB C Immunotherapy Cytotoxicity Tests Immunologic Adoptive Transfer medicine.anatomical_structure Lymphocyte Specific Protein Tyrosine Kinase p56(lck) Lymphocyte Transfusion Sarcoma Experimental Neoplasm Transplantation CD8 T-Lymphocytes Cytotoxic |
Zdroj: | The Journal of Immunology. 164:2214-2220 |
ISSN: | 1550-6606 0022-1767 |
DOI: | 10.4049/jimmunol.164.4.2214 |
Popis: | We have previously reported that CTL were demonstrable early after inoculation of CMS5 fibrosarcoma cells, but that they disappeared within 3 wk. These mice were unable to reject a challenge with CMS5 tumor cells. Other studies demonstrated cell surface phenotype and signaling abnormalities of cells within the spleen. Since we assumed that such an environment would make it more difficult to elicit antitumor immune responses via immunotherapy, we asked whether resection of the tumor could reverse these abnormalities. Although early after tumor cell inoculation tumor resection leads to the development of immunity, the effect at late time points has not been studied critically. To test this, mice were inoculated s.c. with CMS5 cells and after 28 days the tumors were resected. We observed a gradual normalization of the cellular phenotype of the spleen. In particular, there was a decrease in the number of Mac1+/Gr1high cells and an increase in the number of CD3+ cells in the spleen within 24–48 h of tumor resection. By day 10, these values were normal. Levels of p56lck increased as well. The functional implications of these changes were illustrated by the reduced growth rate or the complete rejection of a challenge of tumor cells in the resected mice. Both CD4+ and CD8+ cells were involved in the restoration of tumor immunity. Our results suggested that tumor resection not only led to the reversal of immune suppression, but also unmasked a population of primed T cells able to mediate protective immunity. |
Databáze: | OpenAIRE |
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