Cancer vaccines : from research to clinical practice by Adrian Bot, Mihail Obrocea, Francesco M. Marincola

By Adrian Bot, Mihail Obrocea, Francesco M. Marincola

''Recent advances in immunology and biology have opened new horizons in melanoma treatment, integrated within the increasing array of melanoma treatments, that are immunotherapies, or melanoma vaccines, for either stable and blood borne cancers. melanoma Vaccines: demanding situations and possibilities in Translation is the 1st textual content within the box to carry immunotherapy remedies from the laboratory trial to the bedside for the Read more...

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PD-L1 expression has also been observed in a wide variety of tumors (42). In addition to exhaustion, tumor-specific T cells may become anergic or hyporesponsive. This is due to the lack of co-stimulation as well as presence of various inhibitory cell types at the tumor site (43). Finally, tumors have been shown to secrete factors that attract suppressive cells and/or actively suppress effector cells at the tumor site. This results in a highly immunosuppressive tumor microenvironment making it extremely difficult for antigen-specific cells to become activated.

J Clin Invest 2001; 108: 51–62. 62. Dunn GP, Koebel CM, Schreiber RD. Interferons, immunity and cancer immunoediting. Nat Rev Immunol 2006; 6: 836–48. 63. Gooch JL, Herrera RE, Yee D. The role of p21 in interferon gamma-mediated growth inhibition of human breast cancer cells. Cell Growth Differ 2000; 11: 335–42. 64. Yang Y, Xiang Z, Ertl HC, Wilson JM. Upregulation of class I major histocompatibility complex antigens by interferon gamma is necessary for T-cell-mediated elimination of recombinant adenovirus-infected hepatocytes in vivo.

In addition to CD28, multiple other T-cell surface receptors have co-stimulatory functions, including CD2, CD5, CD30, 4-1BB, OX40 (CD134), inducible co-stimulator (ICOS), and leukocyte function-associated antigen-1. 2/CD86) on APCs. Additionally, CD28 also enhances the expression of other co-stimulatory molecules (such as ICOS, OX40, and 4-1BB), which are important for the formation of memory T cells (3). Conversely, the timely activation of negative regulatory signals in T cells is required to prevent an unduly, inappropriate immune response.

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