LACK OF IL-2 CYTOKINE EXPRESSION DESPITE IL-2 MESSENGER-RNA TRANSCRIPTION IN TUMOR-INFILTRATING LYMPHOCYTES IN PRIMARY HUMAN BREAST-CARCINOMA - SELECTIVE EXPRESSION OF EARLY ACTIVATION MARKERS

Tumor-infiltrating lymphocytes (TIL) are found in most human infiltrat ing ductal breast carcinomas, In studies of other tumors, TIL were cap able of activation by IL-2, both in vitro and in vivo, to produce sele ctive tumor cytolysis, Specific TIL-mediated tumor cytolysis in human breast tumors has recently been reported. The large numbers of TIL wit hin human breast cancers imply that an immune response is occurring, s ince many of these cells express HLA class II as a late activation mar ker. However, the degree of early activation of the native TIL in brea st tumors has not been fully investigated. Early activation markers CD 69, CD43, and CD38 together with the IL-2R (CD25) and IL-2 cytokine we re examined using mAbs and tissue section immunohistology. In situ hyb ridization was used to detect IL-2 mRNA (IL-2 mRNA) in parallel with i mmunohistochemical localization of IL-2. The results revealed the expr ession of CD69, CD43, and CD38, but markedly low CD25 (IL-2R) and IL-2 protein expression by the TIL. This strongly indicates that the TIL a re an activated population of T cells that shows a deficiency in IL-2 protein and IL-2R expression despite adequate levels of IL-2 mRNA. The mechanism for apparent inhibition of IL-2 production and IL-2R expres sion in the presence of IL-2 mRNA is currently unclear; however, this may explain the relative anergic state of native TIL.