On the Topic of IFN Gamma....

My research area is in cancer biology, and I wanted to learn more about the role the immune system plays in cancer suppression. I found what turned out to be a seminal article in the field, about what plays a role in tumor immunogenicity. IFN gamma and lymphocytes prevent primary tumour development and shape tumor immunogenicity (Nature 410, 1107-1111 26 April 2001) talks about the fundamentals we learned in class in the context of cancer biology.
It was previously a school of thought that cancer was "surveillanced", and that this protected a host against tumor development. It was later discovered however, that there were no differences in primary tumor development among athymic nude mice and syngeneic wild type mice. What's more, is that later on it was discovered that nude mice do not actually have completely nonfunctional T cells, but that IFN gamma and perforin play a role in tumor suppression. Now enter Shankaran et al.....
The researchers of this study really defined the details about the roles IFN gamma and lymphocytes play in tumor suppression. The details are really neat.
Two classes of mice (one class was wild type, the other was immunodeficient) were exposed to a chemical carcinogen, and tumor formation was observed. For this study, immunodeficient was defined as individuals who did no express the RAG2 gene, which exists in lymphocytes and plays a role in the recombination of VDJ regions that code for immunoglobins and t-cells. Immunodeficient mice developed more tumors, and developmed them faster. To assess the extent of suppression mechanisms, other classes of mice were compared to the first two- those individuals ranging in different types of deficiencies. The most telling, were the mice which were immunodeficient, AND insensitive to IFNgamma. Those mice had the highest percentage of tumor formation accumulation over everyone.
Other parts of the study included discovering that tumors in immunodeficient mice were more immunogenic than those with normal immune systems. Combined this with the fact that through more experimentation from tumor transplantation, that IFN gamma responsiveness by the tumor cells is critical for immune response, the researchers were able to show that that IFN gamma and STAT1 signaling pathway cooperates to form the immune response.
In a final experiment, researchers wanted to determine the link between lymphocytes and IFN gamma/STAT1 processes. To do this, IFN gamma insensitive tumour cells were expressed in the MHC1 processing components to allow it to be presented so IFN gamma could be upregulated (this part started to go over my head though, sorry if this gets confusing!). These cells were challenged with a virus. Cells which were IFN gamma insensitive required participation of CD4 and CD8 presenting T cells, and those rejected virus and not wild type (please see the paper for clarification on this part). Those cells were also immune to later challenges.
There is a little more to the paper, but I think this is the bulk of it. I found it a very interesting read!