LYMPHOCYTES INFILTRATING COLORECTAL-CANCER HAVE LOW PROLIFERATIVE CAPACITY BUT CAN SECRETE NORMAL LEVELS OF INTERFERON-GAMMA

Significant numbers of infiltrating mononuclear cells are commonly obs erved in solid tumours although their role in restricting tumour growt h is not clear. Tumour-infiltrating lymphocytes (TIL) from 38 patients with colorectal cancer in parallel with peripheral blood lymphocytes (PBL), were assayed to determine their ability to proliferate in respo nse to concanavalin A (ConA) interleukin-2 (IL-1). ConA + IL-2 phorbol 12-myristate 13-acetate (PMA) - ionomycin (IOM) and staphylococcal en terotoxin B (SEB). These reagents were selected to give a ranee of ind ependent of the T cell receptor. Proliferation of TIL was significantl y lower than that of PBL in all cultures: ConA + IL-2 (P < 0.001) PMA + IOM (P < 0.001) SEB (P = 0.002). In addition to the low proliferativ e capacity of TIL production of cytokines by TIL may also play a role in control oi tumour growth. We have assayed IFN gamma production in t he supernatants from 16 paired TIL and PBL cultures and tumour necrosi s factor alpha((TNF-alpha) in 6 paired cultures. TNF alpha concentrati ons were significantly lower in TIL cultures than in PBL cultures stim ulated with ConA (P < 0.05), but no different in control or IL-2 stimu lated cultures. IFN gamma levels did not significantly differ between PBL and TIL cultures, indicating that despite the restricted prolifera tive capacity of TIL, these cells remain capable of secreting signific ant amounts of IFN gamma.