Variation of tumor-infiltrating lymphocytes in human cancers: controversy on clinical significance.

Tumors develop and progress under the influence of a microenvironment comprising a variety of immune cell subsets and their products. Recent studies have shown that tumor-infiltrating lymphocytes (TILs) are not randomly distributed, but organized to accumulate more or less densely in different regions within tumors, and interact with each other. Substantial evidence has suggested that not only CD8(+) and/or CD4(+) αβ T cells but also other lymphocyte subsets, including γδ T cells, B cells, NK cells, and NKT cells, infiltrate tumor tissues in variable quantities and play a key role in the regulation of antitumor immunity. In this article, we summarize available information regarding the diversity and composition of TILs, which may positively or negatively affect tumor growth and patient clinical outcomes. The clinical significance of TILs in human cancers remains unclear and is a subject of considerable controversy; largely due to the lack of functional data for TILs, as well as due to enormous variability of TILs in different tumors. A great deal more functional data about TILs needs to be obtained for individual tumors before TILs can be considered as a prognostic parameter in human cancers.