Vaccines Targeting Tumor Blood Vessel Antigens Promote CD8+ T Cell-Dependent Tumor Eradication or Dormancy in HLA-A2 Transgenic Mice
| العنوان: | Vaccines Targeting Tumor Blood Vessel Antigens Promote CD8+ T Cell-Dependent Tumor Eradication or Dormancy in HLA-A2 Transgenic Mice |
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| المؤلفون: | Xi Zhao, Nina Chi, Ying Cao, Walter J. Storkus, Debabrata Mukhopadhyay, Jennifer L. Taylor, Devin B. Lowe, Peter A. Cohen, Hideho Okada, Anamika Bose, Hideo Komita |
| المصدر: | The Journal of Immunology. 188:1782-1788 |
| بيانات النشر: | The American Association of Immunologists, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Tumor microenvironment, Melanoma, T cell, Immunology, Biology, medicine.disease, medicine.anatomical_structure, Antigen, Cell culture, MHC class I, medicine, biology.protein, Immunology and Allergy, Cytotoxic T cell, CD8 |
| الوصف: | We have recently shown that effective cytokine gene therapy of solid tumors in HLA-A2 transgenic (HHD) mice lacking murine MHC class I molecule expression results in the generation of HLA-A2–restricted CD8+ T effector cells selectively recognizing tumor blood vessel-associated pericytes and/or vascular endothelial cells. Using an HHD model in which HLA-A2neg tumor (MC38 colon carcinoma or B16 melanoma) cells are not recognized by the CD8+ T cell repertoire, we now show that vaccines on the basis of tumor-associated blood vessel Ags (TBVA) elicit protective Tc1-dependent immunity capable of mediating tumor regression or extending overall survival. Vaccine efficacy was not observed if (HLA-A2neg) wild-type C57BL/6 mice were instead used as recipient animals. In the HHD model, effective vaccination resulted in profound infiltration of tumor lesions by CD8+ (but not CD4+) T cells, in a coordinate reduction of CD31+ blood vessels in the tumor microenvironment, and in the “spreading” of CD8+ T cell responses to alternate TBVA that were not intrinsic to the vaccine. Protective Tc1-mediated immunity was durable and directly recognized pericytes and/or vascular endothelial cells flow-sorted from tumor tissue but not from tumor-uninvolved normal kidneys harvested from these same animals. Strikingly, the depletion of CD8+, but not CD4+, T cells at late time points after effective therapy frequently resulted in the recurrence of disease at the site of the regressed primary lesion. This suggests that the vaccine-induced anti-TBVA T cell repertoire can mediate the clinically preferred outcomes of either effectively eradicating tumors or policing a state of (occult) tumor dormancy. |
| تدمد: | 1550-6606 0022-1767 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::7a1b18e7ac0a625ddd31aa72aa82ecd1Test https://doi.org/10.4049/jimmunol.1101644Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi...........7a1b18e7ac0a625ddd31aa72aa82ecd1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15506606 00221767 |
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