FUNCTIONAL-ANALYSIS OF TUMOR-INFILTRATING LEUKOCYTES IN BREAST-CANCERPATIENTS

Background. The immune system is capable of responding to cancer as ev idenced by systemic, regional, and intratumoral leukocyte activation. For individual patients there is no predictable relationship between l eukocyte composition, or function, and the prognosis of the disease. M aterials and methods. Leukocytes from tumor tissues (TIL, n = 17), axi llary lymph nodes (LNL, n = 26), and peripheral blood (PBL, n = 25) of human breast cancer patients were evaluated for the ability to synthe size type 1 cytokines (TNF alpha, IFN gamma, and IL-2) and type 2 cyto kines (IL-4, IL-6, and IL-10) by flow cytometry. The capacity of these cells to mediate in vitro cytotoxicity against the ZR 75-1 breast can cer cell line was simultaneously evaluated. Results. T cells (CD3+) we re the major leukocyte population detected in each tissue with CD4+ ce lls being predominant in TIL, LNL, and PBL. Type 1 cytokines were the predominant type produced by stimulated T cells for each population wi th a statistically greater proportion of IFN gamma+ T cells in TIL as compared with LNL and PBL (P = 0.013 and 0.04, respectively). However, LNL and PBL had a significantly greater proportion of IL2+ T cells as compared with TIL from the same patient (P = 0.02 and 0.01, respectiv ely). The tumoricidal function could be stimulated with recombinant hu man IL-2 in each leukocyte population with substantially higher levels of activity being produced in TIL from node-positive as compared with node-negative patients. Conclusions. This study demonstrates that the re are differences in the capacity of leukocytes from different anatom ical sites of breast cancer patients to synthesize immunostimulatory c ytokines and mediate tumor cell cytotoxicity. Such differences may ref lect prognostically distinct subgroups of patients and might also prov ide a rationale for the development of biological approaches to therap y in selected patients. (C) 1998 Academic Press.