Complete rejection of a T-cell lymphoma due to synergism of T-cell receptor costimulatory molecules, CD80, CD40L, and CD40

Abstract

The equal importance of the qualitative and quantitative characteristics of antigen presentation as well as the set of costimulatory signals provided by antigen presenting cells to T-cells in determining the outcome of T-cell responses at the time of antigen recognition is now clear. Moreover, an important function in innate mechanisms has been recently attributed to costimulatory molecules demonstrating their relevant role in different stages of immune response. In this paper, we demonstrated the ability of CD40L (CD154) and CD80 costimulatory molecules expression in a T-cell lymphoma to induce both T-cell dependent and independent immune responses leading to an important anti-tumor effect. CD40 expression by LBC cells enhanced only T-cell dependent anti-tumor immune response resulting in tumor rejection. Furthermore, this work represents the first report to describe complete tumor rejection after co-inoculation of lymphoma cells transfected with CD40L and CD80 in either presence or absence of CD40 expressing lymphoma cells. In addition, this synergistic effect resulted in long lasting immunity to parental tumor cells. Co-inoculation of tumor cells each genetically modified to express a different costimulatory molecule circumvents the need to co-transfect genetically unstable tumor cells and represents an option for those weakly or non-immunogenic tumors where either treatment alone proved to be inefficient. This strategy represents a promising approach for inducing anti-tumor immunity and provides a new rational design of cancer therapies.