Depression of natural killer cytotoxic activity in lymphocytes infiltrating human pulmonary tumors

Abstract

We assessed natural killer activity of lymphocytes present at the site of human tumors to determine the local effects of the tumor on immune function. Lymphocytes were extracted from human pulmonary tumors of varying histological types. In addition to tumor-infiltrating lymphocytes (TIL), peripheral blood lymphocytes from the same patients were prepared. Using a Michaelis-Menten kinetic model and titration of K562 targets in a 51Cr release assay, TIL exhibited a marked depression of maximal lytic capacity (Vmax) when compared to autologous peripheral blood lymphocytes. In a single cell lysis and binding assay to assess the proportion of target-binding lymphocytes and target-lysing binders, both TIL and peripheral blood lymphocytes had equivalent numbers of lymphocytes binding target cells and an equivalent number of target-binding cells that could mediate cytolysis. Analysis of lymphocyte subsets was performed using mouse monoclonal antibodies. The TIL population expressed markers found on natural killer cells, including HNK-1 and B73.1. Thus, natural killer cells are present at the tumor site, show lytic capability, but appear to be unable to recycle for multiple lytic events.