PULMONARY MACROPHAGES SUPPRESS THE PROLIFERATION AND CYTOTOXICITY OF TUMOR-INFILTRATING LYMPHOCYTES

Adoptive immunotherapy with interleukin-2 and tumor-infiltrating lymph ocytes (TIL) is rarely effective in primary lung cancer. We hypothesiz e that pulmonary macrophages (PM), which are increased substantially i n the lungs of smokers, might suppress TIL function. The addition of P M into the TIL cytotoxicity assay produced a concentration-dependent s uppression of TIL cytotoxicity with up to 71% inhibition of autologous tumor killing at the 1:1 PM:TIL ratio. Inhibition was not target-spec ific, as killing of NK-sensitive (K562), NK-resistant (M14), and autol ogous tumor targets were equally suppressed. Nor was inhibition specif ic for lung TIL, as similar inhibition was observed with melanoma and renal TIL. Using a model system, we demonstrated that both CD3+ antige n-specific and CD56+ nonspecific lymphocytes are susceptible to the su ppressive effects of the PM. Direct co-incubation of PM and TIL for 4 to 44 h resulted in progressive suppression of TIL proliferation and c ytotoxicity. TIL cytotoxicity remained suppressed even if PM were remo ved from the co-culture after 24 h, but was restored if the separated TIL were re-incubated in interleukin-2. These results suggest that PM may locally regulate the proliferative and cytotoxic function of adopt ively transferred TIL.