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 virus genes in the tumor cells and an intense infiltration of leukocytes in the tumor tissue. These infiltrating cells are mainly composed of T lymphocytes and macrophages. The mechanism of this intense infiltration has long been a puzzle. We attempted to address this issue by studying the expression of CC chemokines, which are responsible for recruiting both T cells and macrophages, by an immunohistochemical approach. In biopsies obtained from nasopharynx of 17 NPC patients that contained tumor cells, expression of macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, macrophage chemoattractant protein-1 (MCP-1), MCP-2, MCP-3, and RANTES was detected in the tumor-infiltrating cells, with MIP-1alpha and MCP-1 found in nearly all biopsies and the others relatively less frequently. Furthermore, expression of interferon-gamma (IFN-gamma) was also observed in tumor-infiltrating cells. In contrast, CC chemokines and IFN-gamma were rarely expressed in the 13 control biopsies that were either normal or with nonspecific inflammation, and in 4 biopsies from untreated NPC patients that contained no tumor cells. Using an immunofluorescent double-staining method, MIP-1alpha and MCP-1 were identified to be associated with macrophages, and IFN-gamma with T cells. Moreover, expression of CCR2 and CCR5, the receptors for these chemokines, was also detected in the tumor-infiltrating cells. These data indicate that the intense tumor infiltration by T cells and macrophages is a result of active recruitment. It seems possible that the intense infiltration of leukocytes in NPC tumor tissue is initiated by the activated tumor-reactive 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 macrophages to express CC chemokines, especially MIP-1alpha and MCP-1, which consequently recruit more T cells and macrophages into the tumor tissue.
Tang
K F
KF
Department of Microbiology, Faculty of Medicine, National University of Singapore, Republic of Singapore.
Tan
S Y
SY
Chan
S H
SH
Chong
S M
SM
Loh
K S
KS
Tan
L K
LK
Hu
H
H
D000914:Antibodies, Viral / Q000097:blood; D019742:Chemokines, CC / Q000096:biosynthesis*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007371:Interferon-gamma / Q000096:biosynthesis; D016246:Lymphocytes, Tumor-Infiltrating / Q000737:chemistry / Q000473:pathology; D008264:Macrophages / Q000737:chemistry* / Q000473:pathology; D009303:Nasopharyngeal Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D012367:RNA, Viral / Q000235:genetics; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000096:biosynthesis; D019707:Receptors, Chemokine / Q000096:biosynthesis
D000914:Antibodies, Viral; C515334:CCR2 protein, human; D019742:Chemokines, CC; C099537:Epstein-Barr virus encoded RNA 1; C106732:Epstein-Barr virus encoded RNA 2; D007070:Immunoglobulin A; D012367:RNA, Viral; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D007371:Interferon-gamma