T lymphocytes were isolated from tumor biopsies in 13 patients with breast carcinomas. Immunohistology with monoclonal antibodies confirmed the presence of mononuclear cell infiltrates composed primarily of T lymphocytes in all tumors studied. While the proportion of T lymphocytes expressing the T4 or the T8 surface marker varied from tumor to tumor as determined by morphometric analysis, T8+ cells were more numerous than T4+ cells in 8/12 breast tumors studied. Relatively few T cells (<10% in="" 11/12="" tumors)="" were="" in="" an="" activated="" state="" as="" judged="" by="" the="" surface="" expression="" of="" hla-dr="" antigens="" or="" the="" receptor="" for="" interleukin-2="" (il-2).="" in="" 1="" case="" 20%="" of="" the="" infiltrating="" mononuclear="" cells="" were="" expressing="" the="" il-2="" receptor.="" the="" tumor="" infiltrating="" lymphocytes="" (til)="" recovered="" from="" 10="" tumors="" were="" cloned="" in="" a="" microculture="" system="" that="" permits="" proliferation="" of="" nearly="" 100%="" of="" normal="" peripheral="" blood="" t="" lymphocytes="" (pbl-t).="" in="" contrast="" to="" normal="" and="" autologous="" pbl-t,="" frequencies="" of="" proliferating="" t="" lymphocyte="" precursors="" (ptl-p)="" were="" depressed=""><0.01) in="" 7/10="" til="" preparations="" indicating="" a="" decreased="" responsiveness="" of="" til="" to="" phytohemagglutinin="" at="" the="" single-cell="" level.="" the="" frequency="" of="" ptl-p="" was="" noticeably="" higher="" in="" 2="" cases="" (0.03="" and="" 0.09)="" and="" close="" to="" normal="" in="" 1="" case="">
A total of 170 clones were expanded in vitro and analyzed for different functional capabilities. Most of these clones expressed the T4+/T8-phenotype (73%) and strikingly 53% of these T4+/T8– clones were cytolytic in a lectin-dependent assay, a functional subset which is uncommon among normal PBL-T. Some clones (10%) lysed allogeneic breast tumor cells (MCF7). Only 15% of the clones displayed natural killer activity. Among the cytolytic clones, 17 of 31 tested were also IL-2 producers irrespective of the T4 or T8 phenotype. Our results show that human mammary carcinomas contain many infiltrating T cells with cytolytic potential. Interestingly, among the proliferating cytolytic T cell clones (56% of the microcultures), many expressed the T4+/T8– phenotype. These findings may indicate that the in situ cytolytic reaction (against unknown antigens) is associated preferentially with class II antigens.
Fogarty International Fellow of NIH, 1984–1985; on leave from Dept of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pa, USA