CD8+ Tumor-Infiltrating T Cells Are Trapped in the Tumor-Dendritic Cell Network

Abstract : Chemotherapy enhances the antitumor adaptive immune T cell response, but the immunosuppressive tumor environment often dominates, resulting in cancer relapse. Antigen-presenting cells such as tumor-associated macrophages (TAMs) and tumor dendritic cells (TuDCs) are the main protagonists of tumor-infiltrating lymphocyte (TIL) immuno-suppression. TAMs have been widely investigated and are associated with poor prognosis, but the immuno-suppressive activity of TuDCs is less well understood. We performed two-photon imaging of the tumor tissue to examine the spatiotemporal interactions between TILs and TuDCs after chemotherapy. In a strongly immuno-suppressive murine tumor model, cyclophosphamide-mediated chemotherapy transiently enhanced the antitumor activity of adoptively transferred ovalbumin-specific CD8 + T cell receptor transgenic T cells (OTI) but barely affected TuDC compartment within the tumor. Time lapse imaging of living tumor tissue showed that TuDCs are organized as a mesh with dynamic interconnections. Once infiltrated into the tumor parenchyma, OTI T cells make antigen-specific and long-lasting contacts with TuDCs. Extensive analysis of TIL infiltration on histologic section revealed that after chemotherapy the majority of OTI T cells interact with TuDCs and that infiltration is restricted to TuDC-rich areas. We propose that the TuDC network exerts antigen-dependent unproductive retention that trap T cells and limit their antitumor effectiveness.
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Neoplasia : An International Journal for Oncology Research, Elsevier, 2013, 15 (1), pp.85. 〈10.1593/neo.121572〉
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Alexandre Boissonnas, Fabrice Licata, Lucie Poupel, Sébastien Jacquelin, Luc Fetler, et al.. CD8+ Tumor-Infiltrating T Cells Are Trapped in the Tumor-Dendritic Cell Network. Neoplasia : An International Journal for Oncology Research, Elsevier, 2013, 15 (1), pp.85. 〈10.1593/neo.121572〉. 〈hal-01586881〉

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