Human lung cancer antigen presentation by tumor-associated macrophages to CD4+ lymphocytes from regional nodes

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We investigated whether lung cancer-associated macrophages present tumor antigens to regional lymph node lymphocytes (RLNL), which have been proved to include tumor-reactive T cells. The proliferative response of RLNL to stimulation with tumor-associated macrophages (TAM) was examined by the mixed lymphocyte-macrophage response (MLMR) in 35 patients with primary lung cancer, and alveolar macrophages from normal lung (LM) and peripheral blood monocytes (PBM) were used as controls. The mean stimulation index in response to TMA was higher than that elicited by PBM (11.2 vs. 3.2, p<0.05). In 15 patients additionally tested for RLNL response to autologous tumor cells (mixed lymphocyte-tumor cell reaction (MLTR)), the MLMR to TAM correlated well with the MLTR (p<0.05). The response to these macrophages (RLMR) always involved CD4+ lymphocytes, and was largely abolished by anti-HLA class II antibody. RLNL also frequently responded to autologous macrophages from normal lung (mean stimulation index, 9.0), but the MLMR to LM did not correlate with the MLTR. These results suggest that regional lymph nodes draining lung cancer contain CD4+ T cells, which react with tumor-related antigens in the context of m ajor histocompatibility complex class II. In addition, lung cancer-associated macrophages may present tumor-specific antigen to primed CD4+ T cells.
日本癌病態治療研究会の論文