Thermal regulation of lymphocyte trafficking: hot spots of the immune response

Lymphocytes use extensive vascular networks to traffic to various destinations in the body, including lymphoid organs and extra-lymphoid tissues. This discussion will focus on the emerging evidence that thermal stress regulates the traffic signals that direct the exit of lymphocytes from the vascular freeway. This issue is particularly relevant to T cell-based cancer immunotherapy where delivery of immune effector lymphocytes to neoplastic lesions depends on their extravasation across tumour micro-vessels. Although tumours are frequently highly vascularized by vessels that are competent to support blood flow, the tumour micro-environment has been characterized as non-permissive to lymphocyte extravasation. This may lead to a scenario where limited leukocyte infiltration at tumour sites correlates with a poor prognosis. These observations support the thesis that adjuvant strategies that promote trafficking of tumour-reactive cytolytic leukocytes to tumour sites have the potential to improve the efficacy of immune-based cancer therapy.