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Role of Innate Inflammatory Factors on the Cross Presentation of Tumor Antigens From Apoptotic Cells

Posted on: Thursday, 17 June 2004, 06:00 CDT

Extensive tumor cell death via apoptosis or necrosis takes place in human cancer, either spontaneously or as a consequence of anti- neoplastic therapies. The functional outcome of cross-presentation of tumor antigens from dying tumor cells either results in cross- priming or cross-tolerance. Key mediators of the innate immune response, like pentraxins and the components of the classical complement system, selectively bind to dying cells and modulate phagocytic clearance . In physiological situations the synchronized death of peripheral cells results in a homeostatic response, with production of factors that provide a pathway for safe, anti- inflammatory clearance of cell corpses and debris. This mechanism may as well be involved in tumor escape from immune recognition. We are investigating the transfer of tumor antigens from apoptotic cells to APCs in an in vitro system assessing in particular the role of the prototypic long pentraxin PTX3, of complement fractions (C1q) and the [beta]2 glycoprotein 1 plasma cofactor. We found that cell associated tumor antigen Melan A Mart 1 is efficiently cross presented in vitro by human monocyte derived DC, upon induction of apoptosis. The local availability of inflammatory factors influences the outcome of the interaction between APCs and antigen specific T cells. The molecular characterization of involved pathways is being actively pursued.

P. Baruah1, I. E. Dumitriu1, A. A. Manfredi1, A Mantovani2, V. Russo1, P. Rovere-Querini1

1 Cancer Immunotherapy and Gene Therapy Programme, H San Raffaele- DIBIT, Milan, Italy; 2 Mario Negri Institute and University of Milan, Milan, Italy

Copyright Edizioni Minerva Medica Mar 2004

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