A distinct expression of CC chemokines by macrophages in nasopharyngeal carcinoma: Implication for the intense tumor infiltration by T lymphocytes and macrophages

Nasopharyngeal carcinoma (NPC) is characterized by harboring Epstein-Barr v irus genes in the tumor cells and an intense infiltration of leukocytes in the tumor tissue. These infiltrating cells are mainly composed of T lymphoc ytes and macrophages. The mechanism of this intense infiltration has long b een a puzzle. We attempted to address this issue by studying the expression of CC chemokines, which are responsible for recruiting both T cells and ma crophages, by an immunohistochemical approach. In biopsies obtained from na sopharynx of 17 NPC patients that contained tumor cells, expression of macr ophage inflammatory protein 1 alpha (MIP-1 alpha), MIP-1 beta, macrophage c hemoattractant protein-1 (MCP-1), MCP-2, MCP-3, and RANTES was detected in the tumor-infiltrating cells,,vith MIP-1 alpha and MCP-1 found in nearly al l biopsies and the others relatively less frequently. Furthermore, expressi on of interferon-gamma (IFN-gamma) was also observed in tumor-infiltrating cells. In contrast, CC chemokines and IFN-gamma were rarely expressed in th e 13 control biopsies that were either normal or with nonspecific inflammat ion, and in 4 biopsies from untreated NPC patients that contained no tumor cells. Using an immunofluorescent double-staining method, MIP-1 alpha and M CP-1 were identified to be associated with macrophages, and IFN-gamma with T cells. Moreover, expression of CCR2 and CCR5, the receptors for these che mokines, was also detected in the tumor-infiltrating cells. These data indi cate that the intense tumor infiltration by T cells and macrophages is a re sult of active recruitment. it seems possible that the intense infiltration of leukocytes in NPC tumor tissue is initiated by the activated tumor-reac tive T cells. T cells migrate into the tumor tissue in an antigen-specific mode, and IFN-gamma secreted from these pioneer T cells activates tissue ma crophages; to express CC chemokines, especially MIP-1(alpha and MCP-1, whic h consequently recruit more T cells and macrophages into the tumor tissue. . Copyright (C) 2001 by W.B. Saunders Company