Controversies on the prognostic significance of tumor infiltrating leukocytes in solid human tumors

We have performed immunophenotypical (IP) analyses of tumor infiltrating le ukocytes (TIL) in both childhood brain tumors (medulloblastomas[MEDs]/primi tive neuroectodermal tumors [PNETs] and astrocytomas [ASTRr]) and malignant melanomas (both primary and metastatic) employing a well-characterized lib rary of monoclonal antibodies (MoABs) directed against leukocyte differenti ation/activation associated antigens. The antigens were detected by an indi rect, biotinstreptavidin conjugated alkaline phosphatase (AP) immunocytoche mical technique. Our systematic cell-surface antigen expression profile ana lysis of 76 primary childhood brain armors (34 MEDs/PNETs and 42 ASTRs) ide ntified CD8(+) CTL in 58/76 brain tumors. CD4(+), MHC class II restricted h elper lymphocytes were present in 65/76 brain tumors and represented 1-10% of the observed cells. Macrophages were present in 74/76 childhood brain tu mor cases observed by us. Leukocyte common antigen (LCA) expression was dem onstrated in all 76 brain tumors studied MoAB UJ 308 detected the presence of premyelocytes and mature granulocytes in 60/76 brain tumors. They were l ocalized perivascularly, within the tumor tissue, or close to necrotic regi ons Natural killer (NK) cells were not defined in the childhood brain tumor s observed in this study. The IP characteristics of the heterogeneous leuko cytic infiltrate of 30 primary (PMs) and 10 metastatic melanomas (MMs) was also investigated by us. We established the presence of some type of melano ma infiltrating host's immunological effector cells in all 40 observed mela noma cases. More specifically, we found NK cells, macrophages and granulocy tes in 30/30 PMs and 10/10 MMs. These effector cells represented the vast m ajority (>80%) of the melanoma infiltrating immunocompetent cells. T lympho cytes were observed in 20/30 PMs and 6/10 MMs, but their numbers represente d only between 5% to 10% of the heterogeneous leukocytic infiltrate. B cell s were found in 22/30 PMs and 8/10 MMs, their numbers representing less tha n 5%. Presence of cells of the dendritic reticulum, involved in antigen pre sentation was not determined in any of the observed PMs and MMs. The notion that infiltration of the neoplastically transformed mass of cells by TIL i s always a prognostically positive phenomenon has changed in recent years a s research on extracellular matrix remodeling and angiogenesis have identif ied numerous secreted factors which are common to both neoplastically trans formed cells and infiltrating leukocytes.