Tumor-Infiltrating Lymphocytes and Their Role in Solid Tumor Progression

Tumor-infiltrating lymphocytes (TIL) are an important component of the tumor environment. Their role in tumor growth and progression has been debated for decades. Today, emphasis has shifted to beneficial effects of TIL for the host and to therapies optimizing the benefits by reducing immune suppression in the tumor microenvironment. Evidence indicates that when TILs are present in the tumor as dense aggregates of activated immune cells, tumor prognosis and responses to therapy are favorable. Gene signatures and protein profiling of TIL at the population and single-cell levels provide clues not only about their phenotype and numbers but also about TIL potential functions in the tumor. Correlations of the TIL data with clinicopathological tumor characteristics, clinical outcome, and patients' survival indicate that TILs exert influence on the disease progression, especially in colorectal carcinomas and breast cancer. At the same time, the recognition that TIL signatures vary with time and cancer progression has initiated investigations of TIL as potential prognostic biomarkers. Multiple mechanisms are utilized by tumors to subvert the host immune system. The balance between pro- and antitumor responses of TIL largely depends on the tumor microenvironment, which is unique in each cancer patient. This balance is orchestrated by the tumor and thus is shifted toward the promotion of tumor growth. Changes occurring in TIL during tumor progression appear to serve as a measure of tumor aggressiveness and potentially provide a key to selecting therapeutic strategies and inform about prognosis.