Ubiquitinated Proteins Isolated From Tumor Cells Are Efficient Substrates for Antigen Cross-Presentation
| Autor: | Bernard A. Fox, Hong-Ming Hu, Tarsem Moudgil, Zhihua Cui, Li-Xin Wang, Guangjie Yu, Yongbin Mou |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research Lung Neoplasms T-Lymphocytes medicine.medical_treatment Immunology Lymphocyte Activation Cancer Vaccines Immunotherapy Adoptive Peripheral blood mononuclear cell Viral Matrix Proteins Interferon-gamma 03 medical and health sciences Cross-Priming Lymphocytes Tumor-Infiltrating 0302 clinical medicine Immune system Adjuvants Immunologic Antigen Antigens Neoplasm Carcinoma Non-Small-Cell Lung Cell Line Tumor Aluminum Oxide Autophagy medicine Humans Immunology and Allergy Melanoma Pharmacology Chemistry Cross-presentation Dendritic Cells Immunotherapy Phosphoproteins Ubiquitinated Proteins Cell biology 030104 developmental biology Proteasome Cell culture 030220 oncology & carcinogenesis Ribosomes Ex vivo gp100 Melanoma Antigen |
| Zdroj: | Journal of Immunotherapy. 40:155-163 |
| ISSN: | 1524-9557 |
| DOI: | 10.1097/cji.0000000000000165 |
| Popis: | We have previously shown that inhibition of the proteasome causes defective ribosomal products to be shunted into autophagosomes and subsequently released from tumor cells as defective ribosomal products in Blebs (DRibbles). These DRibbles serve as an excellent source of antigens for cross-priming of tumor-specific T cells. Here, we examine the role of ubiquitinated proteins (Ub-proteins) in this pathway. Using purified Ub-proteins from tumor cells that express endogenous tumor-associated antigen or exogenous viral antigen, we tested the ability of these proteins to stimulate antigen-specific T-cell responses, by activation of monocyte-derived dendritic cells generated from human peripheral blood mononuclear cells. Compared with total cell lysates, we found that purified Ub-proteins from both a gp100-specific melanoma cell line and from a lung cancer cell line expressing cytomegalovirus pp65 antigen produced a significantly higher level of IFN-γ in gp100- or pp65-specific T cells, respectively. In addition, Ub-proteins from an allogeneic tumor cell line could be used to stimulate tumor-infiltrating lymphocytes isolated and expanded from non-small cell lung cancer patients. These results establish that Ub-proteins provide a relevant source of antigens for cross-priming of antitumor immune responses in a variety of settings, including endogenous melanoma and exogenous viral antigen presentation, as well as antigen-specific tumor-infiltrating lymphocytes. Thus, ubiquitin can be used as an affinity tag to enrich for unknown tumor-specific antigens from tumor cell lysates to stimulate tumor-specific T cells ex vivo or to be used as vaccines to target short-lived proteins. |
| Databáze: | OpenAIRE |
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