IMMUNOPATHOLOGY OF METASTASES IN PATIENTS OF COLORECTAL-CARCINOMA TREATED WITH MONOCLONAL-ANTIBODY 17-1A AND GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR

Twenty patients with metastatic colorectal carcinoma were treated with a single infusion (400 mg) of a mouse monoclonal antibody (IgG2a) aga inst the tumor-associated antigen CO 17-1A and with a daily injection of granulocyte macrophage colony-stimulating factor (GM-CSF) for 10 da ys. The cycle was repeated every month, Metastases from 5 of the 20 pa tients biopsied on days 1 and 10 of the first two treatment cycles wer e studied by immunohistochemistry. During treatment, neutrophils, mono cytes, and T lymphocytes increased concordantly in the tumor as in the blood of the individual patient. Macrophages (CD68) and CD8(+) T cell s infiltrated the tumor glands and displayed TIA-1-reactive cytotoxic granules. Neutrophils were seen mainly in areas of necrosis, Activated (HLA-DR+) CD4(+) T cells were usually abundant in the stroma, During treatment, few natural killer cells were found in the tumor, contrary to the marked increase seen in blood. Our observations indicate that G M-CSF markedly recruited activated, tumor-infiltrating leukocytes, pos sibly representing antibody-dependent cellular cytotoxicity and cytoto xic T effector cells, The notion that combined antibody and GM-CSF the rapy may also promote a T-cell antitumor response is further supported and advocated by our findings. The study lends further support to com bining GM-CSF with monoclonal antibody-based therapy.