Mechanisms of lymphocyte traffic in neoplasia

The composition of tumor infiltrating lymphocyte populations is often reported to be different from that of the lymphocyte pool of peripheral blood. This suggests that infiltration-regulating mechanisms reside in or near the tumor microenvironment. Available evidence indicates that these mechanisms exert their effects on lymphocyte traffic. Two models of regulation are proposed. In the selective immigration model, different lymphocyte types display different tendencies to extravasate into the tumor. Selective immigration could reflect heterogeneity of such lymphocyte properties as binding to vascular endothelium, response to chemotactic factors, or spontaneous locomotion. In the other model, selective entrapment, different types of lymphocytes exit from the tumor microenvironment at different rates. Entrapment could be regulated by selectively acting adhesive, locomotion-inhibiting, or negatively chemotactic factors. Available information supporting each model is presented. The composition of infiltrate may also be influenced by the composition of the circulating lymphocyte pool. Evidence is presented that this pool in turn may be influenced by tumor-induced systemic changes in lymphocyte traffic. Deliberate manipulation of lymphocyte traffic should improve the effectiveness of immunotherapeutic regimes. One promising method of traffic manipulation is the modulation of spontaneous motility. A collagen gel assay for spontaneous lymphocyte motility is described.