Variable natural killer function of tumour-infiltrating lymphocytes from breast carcinomas

Abstract

Samples were obtained from 36 breast cancer patients: 24 tissue samples from carcinomas, six samples from non-cancerous breast tissue and 22 samples of peripheral blood (PB). Natural killer (NK) activity was tested against the classical target K-562 and the breast carcinoma cell line T-47D, using a microcytotoxicity assay measuring inhibition of uptake of 3H-thymidine by target cells. The active effector cells against both target cell types were identified as CD-56-positive large granular lymphocytes. PB lymphocytes from breast cancer patients showed normal NK activity against both K-562 (mean inhibition: 75.4%, controls: 78.1%) and T-47D (mean inhibition: 77.6%, controls: 78.0%). Tumour-infiltrating lymphocytes (TIL) from 24 breast carcinomas showed considerable variation in NK activity against K-562: only two cases (8%) had no activity (less than or equal to 5% inhibition), 15 cases (63%) had moderate activity (15-48% inhibition), and seven cases (29%) showed full NK activity (defined as greater than or equal to 50% inhibition). TIL from three carcinomas were also tested against T-47D and gave 21-46% inhibition. The NK activity of TIL declined with time in culture with one notable exception where there was full NK activity after seven days in culture. NK activity of TIL showed significant positive correlation with increasing degree of lymphocytic infiltration of the tumour, and correlated also with PB NK activity. No correlation was apparent with stage of disease. The NK activity was usually lower in the TIL than the PB sample when tested in parallel. This difference was probably caused by experimental conditions as well as different relative numbers of natural killer cells. In six cases tested, infiltrating lymphocytes from carcinoma and normal tissue from the same breast were found to have similar NK activities. We conclude that the non-specific cytotoxic activity of TIL from breast carcinomas covers the whole range from complete lack of function to full capacity comparable with NK activity of PB lymphocytes. The level of activity was moderately correlated with the degree of lymphoid infiltration but was not related to stage of disease. Differences in functional capacity of TIL may be of importance in predicting possible benefits from immunomodulating therapy.