Thesis (Ph.D.) - University of Warwick, 1991.
|Statement||Jennifer Linda Johnson.|
A study of immune responses to ras transformed tumour cells expressing well-defined antigens Author: Johnson, Jennifer Linda ISNI: Awarding Body: University of Warwick Current Institution: University of Warwick Date of Award: Author: Jennifer Linda Johnson. Cancer - Cancer - The immune response to tumours: The autoimmune reaction described above is a negative effect of the immune response to cancer cells, but it does indicate that the body can mount a protective response to cancer. The immune system can identify and destroy emerging cancer cells because it recognizes abnormal antigens on the cell surface as “nonself,” or foreign. The cancer immunity cycle is a model that describes a series of multistep immune events triggered by immunogenic cell death (Fig. ). 10 It commences with the release of tumor antigens that are captured, processed, and presented by antigen-presenting cells (APCs), primarily dendritic cells (DCs), to T-cells in the lymph nodes. This is. Tumour antigens have been explored because they elicit an immune response in patients who have cancer but not in volunteer blood donors or people who do not have cancer. Tumour cells express specific antigens on the cell surface, usually within the MHC molecules.
Despite CD4 + T-cells of being crucial for the maintenance of the immune response through secretion of cytokines, such as IL-2 and IFN-γ, and for playing an important role in anti-tumor effect against genital warts and cervical cancer, studies have shown that the protection against immortalized cells expressing E6 and E7 is more dependent on. The question of what causes the immune response against a tumor‐expressed antigen has not been answered conclusively in any study, mainly due to the lack of suitable assays. Understanding the reason for the immune response against tumor‐expressed antigens also may contribute to an improved understanding of the function of these antigens. Tyler Jacks and colleagues provide a striking example of this process of cancer immunoediting in vivo, showing that tumor-specific antigens (TSAs) are recognized by T lymphocytes, stimulating an immune response to attack the tumor. TSA-expressing sarcomas induced in a K-Ras- and pdeficient background progress much more rapidly when Rag2 is also knocked out, a gene that is essential for the generation of all lymphocytes. This can be done by forcing cancer cells to express their own foreign tumor antigens on MHC Class I to the immune system. Cancer cells often repress expression of MHC Class I proteins by repressing MHC Class I gene transcription. By forcing the cancer cells to present tumor specific or tumor associated antigens, Tc cells can be activated and kill those cells. Alternatively, the total loss of MHC class I .
The RAS mutations are the most frequently occurring somatic mutations in humans, and several studies have established that T cells from patients with RAS-mutant cancer recognize and kill RAS-mutant cells. Enhancing the T cell response via therapeutic cancer vaccination against mutant RAS results in a clinical benefit to patients; thus, T cells specific to RAS mutations are effective at. trate the activation of the adaptive immune response (CD4+ T cells). The immune surveillance of transformed/tumour cells drives alteration of the antigen processing and presentation pathways to evade detection and hence the immune response. Evasion of the immune response is a signiﬁ-cant event tumour development and considered one of the hallmarks of cancer. To avoid immune . Recently, a new CT antigen, NY-ESO-1, has been identified on the basis of spontaneous antibody responses to tumour associated antigens. NY-ESO-1 appears to be one of the most immunogenic antigens known to date, with spontaneous immune responses observed in 50% of patients with NY-ESO-1 expressing cancers. The tumor cell lines used for in vitro stimulation, F10 and the unrelated syngeneic tumor cell line MCA‐, express barely detectable H‐2K b. To facilitate the monitoring of MHC class II‐restricted CD4 T cell responses to tumor antigens, F10 and MCA‐ were modified to express the human MHC class II transactivator (CIITA).