Several APCs participate in apoptotic cell-induced immune modulation. Whether plasmacytoid dendritic cells (PDCs) are involved in this process has not yet been characterized. Using a mouse model of allogeneic bone marrow engraftment, we demonstrated that donor bone marrow PDCs are required for both donor apoptotic cell-induced engraftment and regulatory T cell (Treg) increase. We confirmed in naive mice receiving i.v. syngeneic apoptotic cell infusion that PDCs from the spleen induce ex vivo Treg commitment. We showed that PDCs did not interact directly with apoptotic cells. In contrast, in vivo macrophage depletion experiments using clodronate-loaded liposome infusion and coculture experiments with supernatant from macrophages incubated with apoptotic cells showed that PDCs required macrophage-derived soluble factors—including TGF-β—to exert their immunomodulatory functions. Overall, PDCs may be considered as the major APC involved in Treg stimulation/generation in the setting of an immunosuppressive environment obtained by apoptotic cell infusion. These findings show that like other APCs, PDC functions are influenced, at least indirectly, by exposure to blood-borne apoptotic cells. This might correspond with an additional mechanism preventing unwanted immune responses against self-antigens clustered at the cell surface of apoptotic cells occurring during normal cell turnover.

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Rectal cancer requires a multidisciplinary specialist approach for optimal results. Contact radiotherapy has shown excellent results in T1 N0 disease. A new machine (Papillon 50) should be soon available. Preoperative chemoradiotherapy is the new standard treatment for CT3-CT4 resectable cancer. The local failure rate has dramatically decreased from 30% (20 years ago) down to about 5%. When local failures are disappearing, distant metastases are emerging. The current questions are as follows: 1) How to predict response to chemoradiation to modify the surgical strategy? 2) How to identify patients with high risk of distant metastases to explore more intensive upfront treatments? 3) How to identify the low-risk patient group for which less aggressive treatments may be sufficient?

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