It has been demonstrated previously that platelet-derived CD154 communicates with the adaptive immune compartment, enhancing B and T cell responses in CD154(-/-) mice. The presence of platelets was also shown to be necessary for optimal production of immunoglobulin G (IgG) in normal C57BL/6 mice. These data led us to hypothesize that platelets perform a sentinel function, quickly relaying activating signals to the adaptive immune compartment. Here, we report that platelet-derived CD154 increases serum IgG levels and germinal center formation under conditions where antigen-specific CD4(+) T cell numbers are limiting. We propose that in the physiologic setting where antigen-specific B and T cells are rare, platelets function to enhance signals required for robust adaptive humoral immunity.

Human prostate cancers characteristically express low levels of major histocompatibility complex (MHC) Class I, which makes it challenging to induce protective antitumor responses involving T cells. Here we demonstrate that a whole cell tumor vaccine can induce protective T cell immunity to a low MHC Class I-expressing mouse prostate cancer cell line, RM-1. ALVAC recombinant canarypox viruses encoding interleukin-2, interleukin-12 and tumor necrosis factor-a were used to create therapeutic vaccines in 2 different ways. The RM-1 cells were pre-infected in vitro with the viruses prior to injection (pre-infection vaccine) or the RM-1 cells were injected alone, followed by the viruses (separate injection vaccine). The vaccines were each tested subcutaneously or intradermally. The pre-infection vaccine resulted in 100% clearance of primary tumors, whereas intradermal delivery of the separate injection vaccine cleared 40-60% of primary tumors. Despite the highly efficient primary tumor clearance by the pre-infection vaccine, only the separate injection vaccine generated protection upon rechallenge. Tumor-free survival induced by the separate injection vaccine required natural killer (NK) cells, CD4 1, and CD8 1 T cells. None of these cells alone were sufficient to induce tumor-free survival to the primary challenge, demonstrating an important cooperativity between NK cells and T cells. Secondary clearance of tumors also required NK and CD8 1 T cells, but not CD4 1 T cells. We report for the first time the generation of T cell immunity to the RM-1 prostate cancer cell line, demonstrating that it is possible to generate protective T cell immunity to a MHC I-low expressing tumor. ' 2006 Wiley-Liss, Inc.Key words: T cells; NK cells; prostate cancer; RM-1; ALVAC Prostate cancer is the most frequently diagnosed noncutaneous cancer among men in the United States and the second leading cause of cancer-related deaths.1 Although curative therapy exists for cancer localized to the prostate, only life-prolonging, palliative treatments are available for metastatic prostate cancer.2,3 The generation of systemic immunity to prostate cancer is an alternative approach for developing therapies to prevent and treat metastatic disease. Early immunotherapy studies in solid tumor models showed that tumor cell vaccines expressing cytokines or costimulatory molecules were capable of inducing immunity to tumor cells, otherwise considered nonimmunogenic. [4][5][6][7]

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