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Book ChapterDOI

Escape of human solid tumors from T-cell recognition: molecular mechanisms and functional significance.

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TLDR
This important finding suggests that TAA-specific CTL may be present in some cancer patients but are unable to attack tumor cells due to the presence of inhibitory receptors.
Abstract
Publisher Summary It is known for some time that malignant transformation of human cells may be associated with the appearance of tumor associated antigens (TAA). Decades of research have been aimed at the identification of TAA that can serve as targets for the immunotherapy of malignant diseases. The dramatic progress in the understanding of molecular basis of target cell recognition by cytotoxic T lymphocytes (CTL) has provided the background to design effective strategies to identify TAA recognized by CTL on tumor cells. The extensive application of these strategies by a number of investigators has resulted in the identification of various families of TAA on various types of solid tumors. Mouse tumor models have played an important role in elucidating the mechanisms by which the immune system interacts with tumor cells and eradicates cancer. The second line of evidence is represented by the phenomenon of a “mixed response.” A mixed response occurs rather frequently in patients with metastases, although its actual frequency is not documented. Mixed responses are characterized by the different behavior of synchronous metastases in response to T cell-based immunotherapy. This important finding suggests that TAA-specific CTL may be present in some cancer patients but are unable to attack tumor cells due to the presence of inhibitory receptors.

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Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy.

TL;DR: As the molecular mechanisms of resistance to immunotherapy are elucidated, actionable strategies to prevent or treat them may be derived to improve clinical outcomes for patients.
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Cancer immunotherapy: moving beyond current vaccines.

TL;DR: Results in cancer vaccine trials are considered and alternate strategies that mediate cancer regression in preclinical and clinical models are highlighted.
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Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: A single-arm, multicentre, phase 2 trial

TL;DR: Treatment with atezolizumab resulted in a significantly improved RECIST v1.1 response rate, compared with a historical control overall response rate of 10%, and Exploratory analyses showed The Cancer Genome Atlas (TCGA) subtypes and mutation load to be independently predictive for response to atezolediazepine.
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IFNγ, and lymphocytes prevent primary tumour development and shape tumour immunogenicity

TL;DR: It is shown that lymphocytes and IFNγ collaborate to protect against development of carcinogen-induced sarcomas and spontaneous epithelial carcinomas and also to select for tumour cells with reduced immunogenicity, which explains the apparent paradox of tumour formation in immunologically intact individuals.
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The three Es of cancer immunoediting.

TL;DR: The history of the cancer immunosurveillance controversy is summarized and its resolution and evolution into the three Es of cancer immunoediting--elimination, equilibrium, and escape are discussed.
References
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Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha.

TL;DR: Cultured DCs are as efficient as antigen-specific B cells in presenting tetanus toxoid (TT) to specific T cell clones and their efficiency of antigen presentation can be further enhanced by specific antibodies via FcR- mediated antigen uptake.
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Tolerance, danger, and the extended family.

TL;DR: The possibility that the immune system does not care about self and non-self, that its primary driving force is the need to detect and protect against danger, and that it does not do the job alone, but receives positive and negative communications from an extended network of other bodily tissues is discussed.
Journal ArticleDOI

Genetic instabilities in human cancers

TL;DR: There is now evidence that most cancers may indeed be genetically unstable, but that the instability exists at two distinct levels, and recognition and comparison of these instabilities are leading to new insights into tumour pathogenesis.
Journal ArticleDOI

Phenotypic Analysis of Antigen-Specific T Lymphocytes

TL;DR: Tetramers of human lymphocyte antigen A2 that were complexed with two different human immunodeficiency virus (HIV)-derived peptides or with a peptide derived from influenza A matrix protein bound to peptide-specific cytotoxic T cells in vitro and to T cells from the blood of HIV-infected individuals and correlated well with cytotoxicity assays.
Journal ArticleDOI

A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma

TL;DR: In this paper, a gene was identified that directed the expression of antigen MZ2-E on a human melanoma cell line, which belongs to a family of at least three genes.
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