Analysis of cancer immunceditine in antigen presentation-related molecules and development of treatment to inhibit escape mechanisms of cancer

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(1) Research on human samplesUsing tumor samples from esophageal cancer patients, we found that down-regulation of MHC class I in cancer cells negatively correlated with the infiltration of CD8^+ T cells in cancer tissues and infiltration of CD8^+ T cells in cancer tissues positively correlated with favorable patients' prognosis. These data suggest that CD8^+ T. cells play an important role in immunosurveillance against esophageal cancer and down-regulation of MHC class I can be a mechanism that esophageal cancer cells utilize to escape from immunosurveillance (manuscript in communication).By analyzing 157 lung cancer samples, we found that infiltration of both CDC and CD8^+ T cells in tumor tissue correlated with favorable patients' prognosis. Moreover, tumor expression of MAGE-A4 in advanced lung cancer patients predicted short survival(Int J Oncol, 2006).We engineered T cells to express a chimeric receptor consists of intracellular portion of T cell receptor and antibody against CEA … More . These genetically engineered cells were found to eradicate CEA-expressing autologous colon cancer cells efficiently(Cancer Sci, 2006).We identified promiscuous peptides that can be recognized by NY-ESO-1 specific CD4^+ T cells(Cancer Sci, 2006).We identified CLUAP1 as an Osteosarcoma-related tumor antigen(Int J Oncol, 2007).(2) Research on mouse modelsWe found an importance of the interaction between antigen presenting cells and type I helper T cells in anti-tumor immune responses(Cancer Res, 2006). We also found an important role of type I interferon in cancer vaccine with a toll-like receptor ligand CpG(Int Immunol, 2006).Utilizing tumor antigen-specific TCR transgenic mouse system, we found that tumor progression associated with increased regulatory T cells(Treg) limits the efficacy of adoptive cell therapy with tumor-specific CD8^+ T cells. Stimulation through co-stimulatory receptor GITR reduced Treg and induced effective T cell therapy even in the hosts with progressing tumors(SFCI 2007, CRI symposium in NY 2007, JCA 2007, JSI 2007). These results suggest that the maneuvers to stimulate co-stimulatory receptors such as GITR can be an efficient strategy to inhibit the mechanism of tumor to escape from immunosurveillance leading to an effective immunotherapy Less