{'fraction_non_alphanumeric': 0.035555555555555556, 'fraction_numerical': 0.011851851851851851, 'mean_word_length': 5.233846153846154, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Progress in cancer vaccines by enhanced self-presentation

Early efforts toward human cancer immunotherapy were hindered by the absence of identified antigens to target by vaccination or cell therapy. In the past decade, studies examining CD8+ and CD4+ T cell responses to melanoma and other tumors have uncovered several classes of proteins that give rise to peptides presented by MHC molecules. These include (i) differentiation antigens expressed in the tumor and its normal tissue counterpart e.g., tyrosinase; (ii) cancer-testes antigens expressed in the testes and a variety of malignancies e.g., MAGE-1; and (iii) tumor-specific antigens that arise from mutations in tumor cells e.g., CDK-4 (1–4). The observation that autoimmune depigmentation of the skin (vitiligo) developed in some melanoma patients with tumor regression after IL-2 therapy provided optimism that antigens derived from self-proteins might have utility as targets for immunotherapy (5). Animal model studies demonstrated that T cell immunity could be elicited to tissue-specific self-proteins and promote tumor regression without severe autoimmune injury and provided rationale for clinical vaccine trials targeting self-proteins (6–9). However, with a few exceptions the results of vaccination for human malignancy have been disappointing (10–13). It appears the problem is caused by central and peripheral tolerance mechanisms that limit the repertoire of self-reactive T cells to those of low avidity to prevent autoimmunity, making it difficult to elicit a T cell response sufficient to eradicate tumor (14–16). Recent studies have suggested that the balance between immunity and tolerance is regulated at the immunologic synapse between T cells and specialized bone marrow-derived dendritic cells (DC) that present antigens to T cells (17–19). In a recent issue of PNAS, Fong et al. (20) provide evidence that a key to inducing tumor immunity may lie at this interface. The investigators target carcinoembryonic antigen (CEA), a glycoprotein …