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A new light on tumor immunotherapy for gastric cancer

Dendritic cells (DCs) are professional antigen presenting cells (APCs) that both initiate and modulate the immune response. DCs are cells in the pathway of antigen capture and presentation to T cells, with the unique ability to directly prime nave CD4+ and CD8+ T cells. Gastric cancer is one of the most common cancers. Although gastric cancer therapy has made great progress, it is still difficult to treat advanced gastric cancer, as it has spread to the lymph glands and metastasized. Currently, tumor immunotherapy for gastric cancer has potential. DCs are believed to be essential for stimulating tumor-specific cytotoxic T lymphocyte (CTL) and inducing the protective and therapeutic anti-tumor immunity.

A research team led by Dr. Liang Wang from China investigated whether bone marrow-derived DCs (BM-DCs) pulsed with tumor lysates induce immunity against gastric cancer. Their results will be published on December 14, 2008 in the World Journal of Gastroenterology.

In this study, c-kit+ hematopoietic progenitor cells were magnetically isolated with a MiniMACS separator from BALB/c mice bone marrow cells. These cells were cultured with cytokines GM-CSF, IL-4, and TNF-alpha to induce their maturation. They were analysed by morphological observation, phenotype analysis, and mixed lymphocyte reaction (MLR). BM-DCs were pulsed with tumor cell lysate obtained by rapid freezing and thawing at a 1:3 DC:tumor cell ratio. Finally, CTL activity and interferon-gamma secretion was evaluated ex vivo

They found that c-kit+ hematopoietic progenitor cells from mice bone marrow cells cultured with cytokines for 8 d showed the character of typical mature DCs. However, immature DCs cultured with cytokines for 5 d did not have typical DCs phenotypic markers and could not stimulate allogeneic T cells. Ex vivo primed T cells with SGC-7901 tumor cell lysate-pulsed (TP) DCs were able to induce effective CTL activity against SGC-7901 tumor cells (E:T = 100:1, 69.55% 6.05% specific lysis), but not B16 tumor cells, and produced higher levels of IFN-gamma when stimulated with SGC-7901 tumor cells but not when stimulated with B16 tumor cells (1575.31 60.25 pg/mL in SGC-7901 group vs 164.11 18.52 pg/mL in B16 group, P < 0.01). These results indicated that BM-derived DCs pulsed with tumor lysates can induce anti-tumor immunity specific to gastric cancer ex vivo.


Contact: Lai-Fu Li
World Journal of Gastroenterology

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