Immune response in cancer

It is noteworthy that MHC class I downregulation is not the only escape mechanism available for tumors to avoid T cell responses other mechanisms such as downregulation of the tumor antigens, alterations of the apoptosis program, expression of inhibitory molecules, lack of expression of costimulatory molecules leading to immunological tolerance have been also described. The identification of defined immune escape mechanisms in human or mouse tumors point to the existence of active immunosurveillance which is important for the implementation T cell-based immunotherapy protocols. This information will further help to select patients suitable for such therapies. Furthermore, restoration of the tumor MHC class I phenotype to a normal MHC phenotype may be an other strategy to restore an efficient immune response in cancer patients. All these approaches are still hypothetical and no clinical procedures have been tested so far. 

Cytokines behave as messengers in the immune system. They are secreted by immune cells and can act in an autocrine or a paracrine fashion, functioning either locally or at a distance to modulate immune responses. In cancer therapy, cytokines are often used to enhance immunity. 

Jager E et al. Recombinant vaccinia/fowlpox NY-ESO-1 vaccines induce both humoral and cellular NY-ESO-1-specific immune responses in cancer patients. Proc Natl Acad Sci USA 2006 103 14453-14458. 

Newer uses have appeared in the treatment of viral diseases including AIDS, alteration of the immune response, and cancer. The lithium salt of 7-linolenic acid (LiGLA) has a significant anticancer effect against certain cancers. The neurochemical basis for lithium action is difficult to define. Lithium carbonate induces a wide range of intra- and extracellular changes—most emphasis has been naturally on the similarities with Na/K/Ca/Mg ions. Lithium selectively interferes with the inositol lipid cycle, representing a unified hypothesis of action. The biochemistry, distribution, and cellular localization of lithium has been extensively documented. 

Brichory, F., et al., "Proteomics-Based Identification of Protein Gene Product 9.5 as a Tumor Antigen that Induces a Humoral Immune Response in Lung Cancer," Cancer Res., 61, 7908-7912 (2001). 

IRIV adjuvance in hepatitis A vaccination has been demonstrated as enhancement of humoral responses (1). There are only few adjuvants licensed for human use and they predominantly enhance humoral immune responses (2-4). In view of chronic viral diseases, infections linked to intracellular pathogens, and cancer immunotherapy, there is a need for appropriate adjuvants that have the capability to enhance cellular immune responses, in particular cytotoxic T-cell (CTL) responses (4,5). Here, we addressed IRIV-elicited immune responses and IRIV capacity to enhance CTL responses. 

Although manipulation of the host immune response in animal tumor models has at times yielded impressive therapeutic results, attempts to extend these results to human cancers generally have been disappointing. 

Nam MJ, Madoz-Gurpide J, Wang H, et al. (2003) Molecular profiling of the immune response in colon cancer using protein micro-arrays occurrence of autoantibodies to ubiq-uitin C-terminal hydrolase L3. Proteomics 3, 2108-15. 

Brichory F, Beer D, Le Naour F, Giordano T, Hanash S. (2001) Proteomics-based identification of protein gene product 9.5 as a tumor antigen that induces a humoral immune response in lung cancer. Cancer Res 61, 7908-12. 

It is expected that in the near future antigen-specific vaccines will be applied effectively to induce strong T cell immune responses in patients displaying less progressed stages of disease. A comprehensive discussion on the development of therapeutic cancer vaccines (molecular vaccines) has been presented by Moingeon (2001) and Monzavi-Karbassi and Kieber-Emmons (2001). 

Plotnikov, A., Tichler, T., Korenstein, R. and Keisari, Y. (2005) Involvement of the immune response in the cure of metastatic murine CT-26 colon carcinoma by low electric field enhanced chemotherapy. Int. J. Cancer 117, 816-824. 

Similar to sialic acid, L-fucose is usually displayed as a terminal sugar in glycans allowing it to readily participate in cell-cell interactions and modulate cell motility and migration processes connected with fertilization, embryogenesis, lymphocyte trafficking, immune responses, and cancer metastasis [134,135,136]. To date, many of the specific roles of fucose have been traced... 

Several studies have shown that tumor-specific CD4 T cells play a central role in initiating and maintaining protective immune responses against cancer, and the lack of these T cells in any vaccine strategy could be the cause for weak and transitory immune responses [285,291,326,327]. There are, however, few effective methods for identifying MHC class Il-restricted tumor antigens that can stimulate CD4 T helper cells, and in addition to that, the... 

Waynforth HB, Magee PN. 1974. The effect of N-nitroso-N-methylurea and N-dimethylnitrosamine on cell mediated and humoral immune responses in rats and mice. Br J Cancer 30 512-523. 

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