From the study of tumor cell immunogenicity to the generation of antitumorcytotoxic cells in non-Hodgkin's lymphomas

The question of the immunogenicity of non-Hodgkin's lymphoma (NHL) B cells has been investigated in an attempt to support the development of new immun otherapeutic treatments for this disorder, which remains resistant to conve ntional treatments in most cases. In the present review, we report and disc uss our new findings in the field of NHL B cell immunogenicity. One aspect of our work is the description of the expression and functions of membrane molecules associated with antigen presentation. The expression levels of ad hesion molecules was measured, and the relevance of this expression to the sensitivity of malignant B cells to cell-mediated lysis was studied. Since the T cell response relies on the expression of both HLA class I and II mol ecules, we also investigated whether or not these molecules were present at the surface of NHL B cells. Subsequently, we asked whether antitumor CTL a nd LAK cells could be developed and analyzed the mechanisms of cell lysis i nvolved. Since the generation of a T cell response requires the expression of the costimulatory molecules CD80 and CD86, we investigated their in vivo expression and their modulation in vitro during contact with responding T lymphocytes. The understanding of the immunogenicity of NHL B cells has ena bled us to develop a new culture protocol to induce antitumor specific auto logous CTL. The originality of NHL B cells -unlike most other tumor cells- is to be able to function as antigen presenting cells (APC) and to activate a T cell response in the absence of other professional APC. Over the next few years, these findings should allow the generation of anti-NHL specific T cells for adoptive immunotherapy and or the identification of NHL-associa ted antigens.