Abundant expression of CXCL9 (MIG) by stromal cells that include dendritic cells and accumulation of CXCR3+ T cells in lymphocyte-rich gastric carcinoma.

The neoplastic environment is generally regarded as an immunosuppressive milieu. However, a group of cancers are characterized by the abundance of tumour-infiltrating lymphocytes (TILs). Here we examined the possible roles of chemokines in the formation of lymphoid stroma in lymphocyte-rich gastric carcinomas (GCs), including EBV(+) cases and conventional GCs. Regardless of EBV positivity, TILs in lymphocyte-rich GCs predominantly expressed CXCR3, while its ligand CXCL9 was abundantly expressed by stromal cells and a portion of cancer cells. CXCL9(+) stromal cells were judged to include dendritic cells, because they partly co-expressed fascin, DC-sign, CD83, DC-lamp or HLA-DR. T cells in close contact with CXCL9(+) cells showed frequent labelling of Ki-67 (approximately 10%), suggesting the immunostimulatory activity of CXCL9(+) stromal cells. The T-cell zone of the regional lymph nodes of lymphocyte-rich GCs also abounded with CXCR3(+) T cells and CXCL9(+) stromal cells. This indicated a close similarity between cancer stroma and regional lymph nodes of lymphocyte-rich GCs. Quantitative RT-PCR also confirmed the strong expression of CXCR3, CXCL9 and IFNgamma in lymphocyte-rich GCs. In contrast, conventional GCs contained less abundant CXCR3(+) T cells and few CXCL9(+) stromal cells. Collectively, the CXCL9-CXCR3 axis plays a pivotal role in the formation of lymphoid stroma in lymphocyte-rich GCs. Given similar findings in the regional lymph nodes, the lymphoid stroma of lymphocyte-rich GCs may represent a tertiary lymphoid tissue with predominantly Th1-shifted immune responses.