Stoitzner Patrizia, Green Laura K, Jung Jae Y, Price Kylie M, Atarea Haley, Kivell Bronwyn, Ronchese Franca
Malaghan Institute of Medical Research, Wellington, New Zealand.
Cancer Immunol Immunother. 2008 Nov;57(11):1665-73. doi: 10.1007/s00262-008-0487-4. Epub 2008 Mar 1.
Transplantable B16 melanoma is widely used as a tumor model to investigate tumor immunity. We wished to characterize the leukocyte populations infiltrating B16 melanoma tumors, and the functional properties of tumor-infiltrating dendritic cells (TIDC).
We used the B16 melanoma cell line expressing ovalbumin protein (OVA) to investigate the phenotype and T cell stimulatory capacity of TIDC.
The majority of leukocytes in B16 melanoma were macrophages, which colocalized with TIDCs, B and T cells to the peripheral area of the tumor. Both myeloid and plasmacytoid DC populations were present within tumors. Most of these DCs appeared immature, but about a third expressed a mature phenotype. TIDCs did not present tumor-derived antigen, as they were unable to induce the proliferation of tumor-specific CD4+ and CD8+ T cells in vitro unless in the presence of specific peptides. Some presentation of tumor-derived antigen could be demonstrated in the tumor-draining lymph node using in vivo proliferation assays. However, while proliferation of CD8+ T cells was reproducibly demonstrated, no proliferation of CD4+ T cells was observed.
In summary, our data suggest that DCs in tumors have limited antigen-presenting function. Inefficient antigen presentation extends to the tumor-draining lymph node, and may affect the generation of antitumor immune responses.
可移植的B16黑色素瘤被广泛用作研究肿瘤免疫的肿瘤模型。我们希望对浸润B16黑色素瘤肿瘤的白细胞群体以及肿瘤浸润树突状细胞（TIDC）的功能特性进行表征。
我们使用表达卵清蛋白（OVA）的B16黑色素瘤细胞系来研究TIDC的表型和T细胞刺激能力。
B16黑色素瘤中的大多数白细胞是巨噬细胞，它们与TIDC、B细胞和T细胞共定位于肿瘤的外周区域。肿瘤内同时存在髓样和浆细胞样DC群体。这些DC中的大多数看起来不成熟，但约三分之一表现出成熟表型。TIDC不呈递肿瘤衍生抗原，因为它们在体外无法诱导肿瘤特异性CD4+和CD8+ T细胞增殖，除非存在特定肽段。使用体内增殖试验可在肿瘤引流淋巴结中证明一些肿瘤衍生抗原的呈递。然而，虽然可重复性地证明了CD8+ T细胞的增殖，但未观察到CD4+ T细胞的增殖。
总之，我们的数据表明肿瘤中的DC具有有限的抗原呈递功能。低效的抗原呈递延伸至肿瘤引流淋巴结，并可能影响抗肿瘤免疫反应的产生。
