Functional analysis of tumor-infiltrating leukocytes in breast cancer patients

Abstract

Background: The immune system is capable of responding to cancer as evidenced by systemic, regional, and intratumoral leukocyte activation. For individual patients there is no predictable relationship between leukocyte composition, or function, and the prognosis of the disease.

Materials and methods: Leukocytes from tumor tissues (TIL, n = 17), axillary lymph nodes (LNL, n = 26), and peripheral blood (PBL, n = 25) of human breast cancer patients were evaluated for the ability to synthesize type 1 cytokines (TNF alpha, IFN gamma, and IL-2) and type 2 cytokines (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 cancer cell line was simultaneously evaluated.

Results: To cells (CD3+) were the major leukocyte population detected in each tissue with CD4+ cells being predominant in TIL, LNL, and PBL. Type 1 cytokines were the predominant type produced by stimulated T cells for each population with 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, respectively). The tumoricidal function could be stimulated with recombinant human 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 there are differences in the capacity of leukocytes from different anatomical sites of breast cancer patients to synthesize immunostimulatory cytokines and mediate tumor cell cytotoxicity. Such differences may reflect prognostically distinct subgroups of patients and might also provide a rationale for the development of biological approaches to therapy in selected patients.