1.There is an interesting and surprising new study published in this month's JCI by the NCI's all star immunotherapy team: Microbial translocation augments the function of adoptively transferred self/tumor-specific CD8+ T cells via TLR4 signaling
Chrystal M. Paulos1, Claudia Wrzesinski1, Andrew Kaiser,1, Christian S. Hinrichs1, Marcello Chieppa2, Lydie Cassard1, Douglas C. Palmer1, Andrea Boni1, Pawel Muranski1, Zhiya Yu1, Luca Gattinoni1, Paul A. Antony3, Steven A. Rosenberg1 and Nicholas P. Restifo1 J. Clin. Invest. 117:2197-2204 (2007). doi:10.1172/JCI32205.J. Clin. Invest. 117:2197-2204 (2007). doi:10.1172/JCI32205.
2. The NCI has previously reported using chemotherapy and whole body radiation to deplete regulatory T cells and "cytokine sinks" prior to infusing their adoptive genetically modified T cells primed against a gp 100 antigen in their remarkably successful end stage melanoma therapy.The new study reports that the major positive effect of whole body radiation may be its impact on microbes in the gut, increasing the level of LPS, which is a powerful stimulant of the innate immune system. Administration of ultrapure LPS to non irradiated mice increased immune activity against established tumors and further enhanced tumor remissions when given to irradiated mice.
3. This was a particularly interesting observation: "Our finding that microbial translocation augments the function of adoptively transferred CD8+ T cells brings to mind findings reported by William B. Coley over a century ago (47). Hypothesizing that tumor regression in some patients was the result of bacterial infection, Coley designed a mixture of bacteria consisting of killed cultures of Streptococci and Bacillus prodigiosus known as Coley’s toxins. He reported occasional success using these toxins in patients with cancer. Our findings may be consistent with the notion that activation of the innate immune system can trigger tumor regression with bacterially derived products."
4. While tangential to this article, Dr. Petrylak's presentation of Taxotere after Provenge last November also stated that Taxotere preciptates a macrophage innate immune response. In any event, it is a fascinating analyis coming from an unexpected source and potentially a quite positive future element in all immunotherapies.
