CD40 activation of carcinoma cells increases expression of adhesion and major histocompatibility molecules but fails to induce either CD80/CD86 expression or T cell alloreactivity

A major obstacle for the development of cancer immunotherapy is the poor ca pacity of most tumor cells to present antigen. It has previously been shown that ligation of CD40 on the surface of malignant B cells results in the i nduction of efficient antigen presentation primarily because of upregulated expression of MHC, costimulatory, and adhesion molecules. Ongoing clinical trials are testing the impact of CD40 ligation as immunotherapy for B cell malignancies. Because CD40 is also widely expressed in carcinomas, we stud ied whether CD40 activation of these cells using soluble recombinant trimer ic human CD40 ligand (srhCD40L) can also induce T cell responses. Here, we show that carcinoma cells upregulate expression of CD54 and MHC molecules f ollowing in vitro exposure to srhCD40L but do not upregulate CD80 or CD86. CD40-activated carcinoma cells failed to trigger mixed lymphocyte reactions , in sharp contrast to CD40-activated lymphoma cells for which CD40 activat ion, as expected, resulted in increased expression of MHC, adhesion, and co stimulatory molecules, and generated brisk allogeneic lymphocyte reactions. Retroviral-mediated expression of CD80 in carcinoma cells, with or without CD40 activation, triggered mixed lymphocyte reactions, provided cells were treated with IFN-gamma. Thus, the cell surface phenotype induced on carcin oma cells followina CD40 activation is not fully capable of inducing T cell proliferation; however, these results support ongoing efforts to exploit c ostimulation in clinical efforts aimed at increasing carcinoma immunogenici ty.