Gene expression and immune cell profiles in oral squamous cell carcinoma: Insights into lymphatic metastasis

Metastasis is the most deadly event in cancer progression, but the cells which initiate a metastasis require a specialized set of survival skills. The progressive clonal evolution model of cancer development was previously assumed to apply to metastatic ability, but recent work has shown that distant metastatic ability may be acquired much earlier in the life of the primary tumor. We used human oral squamous cell carcinoma as a model to determine whether the ability to metastasize to lymph nodes could be determined from the genetic profile of the primary tumor using microarray analysis in a small cohort of patients, and found that metastatic primary tumors could be discriminated from nonmetastatic primary tumors based upon their genetic profile, supporting the hypothesis that metastatic ability is an early rather than a late event in tumor development. Since tumor genetics are likely to affect interactions with the immune system, which may play a role in the tumor\u27s ability to metastasize, we investigated on a larger scale the interactions of various dendritic cell subsets with the primary tumor to determine if the presence and/or abundance of these subsets were correlated with metastasis, survival, and other prognostic factors using immunohistochemistry. We did not find that presence and/or abundance of any dendritic cell subsets were correlated with metastasis, but several were correlated with survival and other prognostic factors, showing that the complex interactions between these cells and the primary tumors have clinical relevance although their specific roles are yet unknown. Although the dendritic cell response at the primary tumor was comprehensively dysfunctional, we found evidence of two different immune responses in the lymph nodes of metastatic versus nonmetastatic patients, suggesting that although the immune response at the primary tumor may not be intimately involved with metastatic ability, the regional immune system is not ignorant of the tumor