Antitumor effector cells: extravasation and control of metastasis.

To develop effective antimetastatic response, effector cells have to reach the tissue site of tumor metastasis. Different lymphocyte subsets vary in their ability to extravasate and reach sites of tissue injury or tumor growth. The ability of lymphoid cells to extravasate is a function of several different parameters, including cellular activation state and ability to release cytokines, proteolytic enzymes or to respond to chemotactic stimuli present in the tumor microenvironment. Adoptively transferred effector cells can only be therapeutically effective if they extravasate, reach the tumor or its microenvironment and interfere with tumor growth or metastasis. A large number of events that might be involved in accumulation of effector cells such as, e.g., A-NK cells in tumor metastases, are illustrated in the schema in Figure 3. The future challenge will be to gain an in-depth understanding of these events, including effector cell migration and extravasation, to assure optimal transfers of these cells to patients with metastatic disease.