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Camouflage and Sabotage; Tumor escape from Immune Surveillance

Professor Rolf Kiessling
Cancer Center Karolinska
Dept. of Oncology-Pathology
Karolinska Instituttet
Stockholm, Sweden

Time: 2009, Monday the 9th of March, 14.30

Place: "Lille Auditorium", Herlev University Hospital, Herlev Ringvej 75, DK-2730 Herlev

It would be nice to welcome you all

Per thor Straten
Director

Abstract

Camouflage and sabotage; Tumor escape from Immune Surveillance

Professor Rolf Kiessling
Cancer center Karolinska, Karolinska Institutet, Stockholm, Sweden

Therapeutic vaccination remains to be established as a clinical treatment modality for cancer. Although immunization strategies have often been successful in eliciting tumor antigen-specific T cell responses in at least a portion of the immunized patients, these responses are often not accompanied by a clinical regression of disease or significant improvement in patient survival. The underlying causes behind this failure of the immune system to eliminate established tumor burdens are multiple, and range from mechanisms conferring tumor target resistance as well as a compromised immune system in the cancer patient. As an example of the former mechanism, the majority of human tumors develop defects in their antigen processing machinery (APM), making them invisible to tumor specific cytotoxic T cells. Ovarian carcinomas typically manifest these abnormalities and generally have low levels of MHC class I expression as well as defects in various components in the APM machinery, thus concealing the tumour cells from cytolysis by MHC class I restricted cytotoxic T cells. Tumors expressing low levels of of MHC class I can instead be targeted by NK cells, and freshly isolated ovarian cancer cells express activating NK ligands which can effectively activate NK cells for tumor cell elimination. Moreover, the problem of overcoming the phenomenon of “tumor induced immune dysfunctions” remains a major challenge to immunotherapy in patients with advanced cancer. The role of the “myeloid suppressor cell” (MSC) in this phenomenon and the deleterious effects of oxidative stress on T cells are essential issues in this respect. The ability of oxidative stress to selectively target memory CD8 T cells as well as the NK dim subset, which are the lymphocyte subsets most active in tumor cytolysis, while sparing T regulatory cells constitutes a major challenge for immunotherapy based on T cells or NK cells. Approaches to “arm” cytolytic T cells and NK cells by gene-therapy approaches against the deleterious effects of tumor induced immune suppression will be discussed.

Download invitation and abstract: seminar March 9, 2009 , MS Word, 94 kb

Last update: February 16, 2009